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第7行：
第7行： − 人工细胞、人工合成细胞或最小细胞是一种模仿生物细胞单个或多个功能的工程粒子。通常，人工细胞是包裹生物活性物质的生物膜或聚合物膜。因此，脂质体、聚合物泡囊、纳米微粒、微胶囊和其他一些颗粒可以被定性为人工细胞。+ 第226行：
第226行： − 人工细胞包埋法研究的第一种酶是治疗小鼠淋巴肉瘤的天冬酰胺酶。这种治疗延缓了肿瘤的发生和生长。这些初步的发现导致了在酪氨酸依赖性黑色素瘤中使用人工细胞进行酶传递的进一步研究。这些肿瘤的生长比正常细胞更依赖于酪氨酸，研究表明，降低小鼠全身酪氨酸水平可以抑制黑色素瘤的生长。利用人工细胞输送酪氨酸酶和消化酪氨酸的酶，可以提高酶的稳定性，并且能有效地去除酪氨酸，而不会产生与饮食中酪氨酸恶化有关的严重副作用。+ 第270行：
第270行： − + − + − 细胞封装在人工膜内的示意图。+ 第284行：
第284行： − 最常用的制备人造细胞的方法是通过细胞包囊。封装细胞通常是通过从液体细胞悬浮液中产生控制尺寸的液滴来实现的，然后快速凝固或凝胶化以提供额外的稳定性。稳定化可以通过温度的变化或材料的交联来实现。细胞在封装时看到的微环境变化。它通常从单分子层到悬浮在聚合物膜内的聚合物支架上。这种技术的缺点是封装细胞会降低其生存能力以及增殖和分化能力。此外，在微囊中待一段时间后，细胞会形成团簇，抑制氧气和代谢废物的交换，导致细胞凋亡和坏死，从而限制细胞的功效，激活宿主的免疫系统。人造细胞已经成功地移植了一些细胞，包括治疗糖尿病的胰岛、甲状旁腺细胞和肾上腺皮质细胞。+ − + + + 第293行：
第295行： − 器官捐献者的短缺使人造细胞成为治疗肝衰竭的替代疗法的关键。人工肝细胞用于肝细胞移植已被证实在动物肝病模型和生物人工肝装置中提供肝功能的可行性和有效性。实验中，肝细胞被附着在微载体表面，然后进化成肝细胞，包裹在由聚赖氨酸外皮覆盖的海藻酸钠微滴中的三维基质中。这种给药方法的一个关键优势是在治疗期间避免了免疫抑制治疗。肝细胞包囊已被提议用于生物人工肝。该装置由一个嵌有分离肝细胞的圆柱形腔室组成，病人的血浆通过这个腔室在一种血液灌流中循环。由于微囊具有很高的比表面积和体积比，它们为基质扩散提供了较大的表面积，并且可以容纳大量的肝细胞。对诱导性肝衰竭小鼠的治疗显示存活率显著提高。人工肝系统仍处于早期发展阶段，但对于等待器官移植或者病人自身的肝脏重新充分恢复正常功能的病人来说，显示出了潜力。迄今为止，使用人工肝系统和肝细胞移植治疗终末期肝病的临床试验已经显示健康指标的改善，但尚未提高存活率。移植后人工肝细胞的短寿命和聚集是目前肝移植面临的主要障碍。与干细胞共包裹的肝细胞在培养中表现出更大的生存能力，植入和植入人工干细胞后也表现出肝再生。因此，利用干细胞来包裹再生医学细胞的研究引起了人们的兴趣。+ − + + + − 有人提出口服活菌落，目前正用于治疗肠道菌群的调节、预防腹泻疾病、治疗幽门螺杆菌感染、过敏性炎症、乳糖不耐症和免疫调节等。拟议的作用机制尚未得到充分理解，但被认为具有两个主要作用。首先是营养效应，即细菌与产毒细菌竞争。第二是卫生效应，刺激抵抗定殖和免疫反应。细菌培养物的口服给药通常是一个问题，因为它们是免疫系统的目标，通常在口服时被破坏。人工细胞通过向体内提供模仿和选择性或长期释放，从而提高进入胃肠道系统的细菌的生存能力，从而帮助解决这些问题。此外，可以设计活细菌包囊，使小分子(包括多肽)扩散到体内用于治疗目的。已被证明成功用于细菌传递的膜包括醋酸纤维素和海藻酸盐的变体。其他用途包括保护细菌细胞免受结核分枝杆菌的攻击和免疫系统分泌免疫球蛋白的增加。该技术受到系统性感染、不良代谢活动和基因转移风险的限制。然而，更大的挑战仍然是如何将足够多的有生命的细菌运送到感兴趣的部位。+ − + 第311行：
第315行： − 人造血细胞作为氧载体被用作一种红细胞替代品，尽管它们缺乏红细胞的其他成分。它们由合成的聚合物或人工膜包裹在纯化的动物、人或重组的血红蛋白周围。总的来说，血红蛋白的输送仍然是一个挑战，因为它在没有任何修饰的情况下输送时是剧毒的。在一些临床试验中，已经观察到血管升压效应。+ − + 第322行：
第326行： − 人造红细胞在1980年代的艾滋病恐慌之后，人们对使用人造红细胞制造血液产生了研究兴趣。除了避开疾病传播的可能性，人造红细胞也是人们所需要的，因为它们可以消除与同种异体输血相关的缺点，如血型鉴定、免疫反应及其短暂的42天储存期。血红蛋白替代物可以存放在室温下，而不是在冷藏条件下存放一年以上。人们已经尝试开发出一种完整工作的红细胞，它不仅包含碳酸，而且包含氧载体和与细胞相关的酶。第一次尝试是在1957年，用超薄聚合物膜代替红细胞膜，然后通过脂质膜和最近的可生物降解聚合物膜进行封装。包含脂质和相关蛋白质的生物红细胞膜还可以通过绕过巨噬细胞摄取和系统清除来包裹纳米颗粒和增加体内停留时间。+ + + − = = = = = 人工白细胞聚合体是一种具有白细胞粘附特性的聚合体。聚合体是由双层薄片组成的囊泡，可以包裹许多活性分子，如药物或酶。通过将白细胞的粘附特性添加到细胞膜上，白细胞可以减慢速度，或者在快速流动的循环系统内沿着上皮细胞壁滚动。+ + + 第337行：
第345行： − 非常规类型的人造细胞电子人造细胞的概念在2004年至2015年由约翰 · 麦卡斯基尔协调的一系列欧盟项目中得到扩展。+ 第343行：
第351行： − 2004年至2008年，欧洲联盟委员会赞助制定了可编程人造细胞进化方案，其目标是为最终融入信息系统奠定基础，创建”由简单的有机和无机物质构成的微观自组织、自我复制和可进化的自主实体，这些物质可通过遗传程序进行编程，以履行特定功能”。PACE 项目开发了第一台欧米茄机器，这是一种人工细胞的微流体生命支持系统，可以补充化学缺失的功能(最初由诺曼 · 帕卡德、斯蒂恩 · 拉斯穆森、马克 · 比多和约翰 · 麦卡斯基尔提出)。最终目标是在复杂的微型可编程环境中实现可进化的混合细胞。欧米茄机器的功能可以逐步删除，对人造细胞化学提出了一系列可解决的进化挑战。该项目实现了人工细胞三个核心功能(遗传子系统、包容系统和新陈代谢系统)成对的化学整合，并为包容和基因扩增的整合创造了新的空间分辨可编程微流体环境。这个项目导致了欧洲生物技术中心的建立。+ 第355行：
第363行： − 这种方法的主要局限性，除了最初在掌握微观电化学和电动力学方面的困难之外，是电子系统作为一个刚性的非自治的宏观硬件相互连接。2011年，麦卡斯基尔提议颠倒电子学和化学的几何学: 不把化学物质放在活跃的电子介质中，而是把微观的自主电子学放在化学介质中。他组织了一个项目，以解决第三代100微米规模的电子人造细胞问题，这种细胞可以由两个半细胞”实验室”自我组装，以封闭内部化学空间，并借助浸入其中的有源电子设备发挥功能。这些细胞可以复制它们的电子和化学成分，并且能够在它们特殊的预合成微观构件所提供的约束条件下进化。2012年9月，这个项目开始了工作。+ − + 第364行：
第372行： − = = = Jeewanu = = = Jeewanu 原细胞是具有细胞样结构的合成化学粒子，似乎具有一些功能性的活性。1963年首次在阳光下由简单矿物质和基本有机物合成，据报道它仍然具有一些新陈代谢能力，包括半透膜、氨基酸、磷脂、碳水化合物和类 rna 分子。然而，Jeewanu 的性质和属性仍有待澄清。+ − + − + − + − + − + − + − − * Protocell − * Synthetic biology − * Artificial life − * Targeted drug delivery − * Respirocyte − * Chemoton − * Jeewanu − * Build-a-Cell − 原细胞合成生物学人工生命靶向药物输送呼吸细胞+ + + + + + + +
→= = = 封装细胞 = = =
An artificial cell, synthetic cell or minimal cell is an engineered particle that mimics one or many functions of a biological cell. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such, liposomes, polymersomes, nanoparticles, microcapsules and a number of other particles can qualify as artificial cells.
An artificial cell, synthetic cell or minimal cell is an engineered particle that mimics one or many functions of a biological cell. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such, liposomes, polymersomes, nanoparticles, microcapsules and a number of other particles can qualify as artificial cells.
人工细胞、人工合成细胞或最小细胞是一种模仿生物细胞单个或多个功能的工程粒子。通常，人工细胞是包裹生物活性物质的生物膜或聚合物膜。因此，脂质体、高分子囊泡、纳米微粒、微胶囊和其他一些颗粒可以被定性为人工细胞。
The terms "artificial cell" and "synthetic cell" are used in a variety of different fields and can have different meanings, as it is also reflected in the different sections of this article. Some stricter definitions are based on the assumption that the term "cell" directly relates to [[Cell (biology)|biological cells]] and that these structures therefore have to be alive (or part of a living organism) and, further, that the term "artificial" implies that these structures are artificially built from the bottom-up, i.e. from basic components. As such, in the area of [[synthetic biology]], an artificial cell can be understood as a completely synthetically made cell that can capture [[energy]], maintain [[electrochemical gradient|ion gradients]], contain [[macromolecule]]s as well as store information and have the ability to [[replicate (biology)|replicate]].<ref>{{cite journal|vauthors=Deamer D|date=July 2005|title=A giant step towards artificial life?|journal=Trends in Biotechnology|volume=23|issue=7|pages=336–338|doi=10.1016/j.tibtech.2005.05.008|pmid=15935500}}</ref> This kind of artificial cell has not yet been made.
The terms "artificial cell" and "synthetic cell" are used in a variety of different fields and can have different meanings, as it is also reflected in the different sections of this article. Some stricter definitions are based on the assumption that the term "cell" directly relates to [[Cell (biology)|biological cells]] and that these structures therefore have to be alive (or part of a living organism) and, further, that the term "artificial" implies that these structures are artificially built from the bottom-up, i.e. from basic components. As such, in the area of [[synthetic biology]], an artificial cell can be understood as a completely synthetically made cell that can capture [[energy]], maintain [[electrochemical gradient|ion gradients]], contain [[macromolecule]]s as well as store information and have the ability to [[replicate (biology)|replicate]].<ref>{{cite journal|vauthors=Deamer D|date=July 2005|title=A giant step towards artificial life?|journal=Trends in Biotechnology|volume=23|issue=7|pages=336–338|doi=10.1016/j.tibtech.2005.05.008|pmid=15935500}}</ref> This kind of artificial cell has not yet been made.
The first enzyme studied under artificial cell encapsulation was asparaginase for the treatment of lymphosarcoma in mice. This treatment delayed the onset and growth of the tumor. These initial findings led to further research in the use of artificial cells for enzyme delivery in tyrosine dependent melanomas. These tumors have a higher dependency on tyrosine than normal cells for growth, and research has shown that lowering systemic levels of tyrosine in mice can inhibit growth of melanomas. The use of artificial cells in the delivery of tyrosinase; and enzyme that digests tyrosine, allows for better enzyme stability and is shown effective in the removal of tyrosine without the severe side-effects associated with tyrosine depravation in the diet.
The first enzyme studied under artificial cell encapsulation was asparaginase for the treatment of lymphosarcoma in mice. This treatment delayed the onset and growth of the tumor. These initial findings led to further research in the use of artificial cells for enzyme delivery in tyrosine dependent melanomas. These tumors have a higher dependency on tyrosine than normal cells for growth, and research has shown that lowering systemic levels of tyrosine in mice can inhibit growth of melanomas. The use of artificial cells in the delivery of tyrosinase; and enzyme that digests tyrosine, allows for better enzyme stability and is shown effective in the removal of tyrosine without the severe side-effects associated with tyrosine depravation in the diet.
人工细胞包裹法研究的第一种酶是治疗小鼠淋巴肉瘤的天冬酰胺酶。这种治疗延缓了肿瘤的发生和生长。这些初步的发现导致了在酪氨酸依赖性黑色素瘤中使用人工细胞进行酶传递的进一步研究。这些肿瘤的生长比正常细胞更依赖于酪氨酸，研究表明，降低小鼠全身酪氨酸水平可以抑制黑色素瘤的生长。利用人工细胞输送酪氨酸酶和消化酪氨酸的酶，可以提高酶的稳定性，并且能有效地去除酪氨酸，而不会产生与饮食中酪氨酸恶化有关的严重副作用。
Artificial cell enzyme therapy is also of interest for the activation of [[prodrugs]] such as [[ifosfamide]] in certain cancers. Artificial cells encapsulating the [[cytochrome p450]] enzyme which converts this prodrug into the active drug can be tailored to accumulate in the pancreatic carcinoma or implanting the artificial cells close to the tumor site. Here, the local concentration of the activated ifosfamide will be much higher than in the rest of the body thus preventing systemic [[toxicity]].<ref name='Lohr'>{{cite journal | vauthors = Löhr M, Hummel F, Faulmann G, Ringel J, Saller R, Hain J, Günzburg WH, Salmons B | display-authors = 6 | title = Microencapsulated, CYP2B1-transfected cells activating ifosfamide at the site of the tumor: the magic bullets of the 21st century | journal = Cancer Chemotherapy and Pharmacology | volume = 49 | issue = Suppl 1 | pages = S21-S24 | date = May 2002 | pmid = 12042985 | doi = 10.1007/s00280-002-0448-0 | s2cid = 10329480 }}</ref> The treatment was successful in animals<ref>{{cite journal | vauthors = Kröger JC, Benz S, Hoffmeyer A, Bago Z, Bergmeister H, Günzburg WH, Karle P, Klöppel G, Losert U, Müller P, Nizze H, Obermaier R, Probst A, Renner M, Saller R, Salmons B, Schwendenwein I, von Rombs K, Wiessner R, Wagner T, Hauenstein K, Löhr M | display-authors = 6 | title = Intra-arterial instillation of microencapsulated, Ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting | journal = Pancreatology | volume = 3 | issue = 1 | pages = 55–63 | year = 1999 | pmid = 12649565 | doi = 10.1159/000069147 | s2cid = 23711385 }}</ref> and showed a doubling in median survivals amongst patients with advanced-stage [[pancreatic cancer]] in phase I/II clinical trials, and a tripling in one-year survival rate.<ref name=Lohr/>
Artificial cell enzyme therapy is also of interest for the activation of [[prodrugs]] such as [[ifosfamide]] in certain cancers. Artificial cells encapsulating the [[cytochrome p450]] enzyme which converts this prodrug into the active drug can be tailored to accumulate in the pancreatic carcinoma or implanting the artificial cells close to the tumor site. Here, the local concentration of the activated ifosfamide will be much higher than in the rest of the body thus preventing systemic [[toxicity]].<ref name='Lohr'>{{cite journal | vauthors = Löhr M, Hummel F, Faulmann G, Ringel J, Saller R, Hain J, Günzburg WH, Salmons B | display-authors = 6 | title = Microencapsulated, CYP2B1-transfected cells activating ifosfamide at the site of the tumor: the magic bullets of the 21st century | journal = Cancer Chemotherapy and Pharmacology | volume = 49 | issue = Suppl 1 | pages = S21-S24 | date = May 2002 | pmid = 12042985 | doi = 10.1007/s00280-002-0448-0 | s2cid = 10329480 }}</ref> The treatment was successful in animals<ref>{{cite journal | vauthors = Kröger JC, Benz S, Hoffmeyer A, Bago Z, Bergmeister H, Günzburg WH, Karle P, Klöppel G, Losert U, Müller P, Nizze H, Obermaier R, Probst A, Renner M, Saller R, Salmons B, Schwendenwein I, von Rombs K, Wiessner R, Wagner T, Hauenstein K, Löhr M | display-authors = 6 | title = Intra-arterial instillation of microencapsulated, Ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting | journal = Pancreatology | volume = 3 | issue = 1 | pages = 55–63 | year = 1999 | pmid = 12649565 | doi = 10.1159/000069147 | s2cid = 23711385 }}</ref> and showed a doubling in median survivals amongst patients with advanced-stage [[pancreatic cancer]] in phase I/II clinical trials, and a tripling in one-year survival rate.<ref name=Lohr/>
====Encapsulated cells====
====Encapsulated cells====
= = = = 封装细胞 = = = =
= = = = 微囊细胞 = = = =
[[File:Cell capsule schematic.png|thumb|300px|Schematic representation of encapsulated cells within artificial membrane.细胞封装在人工膜内的示意图。|链接=Special:FilePath/Cell_capsule_schematic.png]]
[[File:Cell capsule schematic.png|thumb|300px|Schematic representation of encapsulated cells within artificial membrane.人工膜内微囊细胞的原理图表示。|链接=Special:FilePath/Cell_capsule_schematic.png]]
thumb|300px|alt=Schematic of cells encapsulated within an artificial membrane.|Schematic representation of encapsulated cells within artificial membrane.
thumb|300px|alt=Schematic of cells encapsulated within an artificial membrane.|Schematic representation of encapsulated cells within artificial membrane.
人工膜内微囊细胞的原理图表示。
The most common method of preparation of artificial cells is through [[cell encapsulation]]. Encapsulated cells are typically achieved through the generation of controlled-size droplets from a liquid cell [[Suspension (chemistry)|suspension]] which are then rapidly solidified or gelated to provide added stability. The stabilization may be achieved through a change in temperature or via material crosslinking.<ref name=Prakash/> The microenvironment that a cell sees changes upon encapsulation. It typically goes from being on a [[monolayer]] to a suspension in a polymer scaffold within a polymeric membrane. A drawback of the technique is that encapsulating a cell decreases its viability and ability to proliferate and differentiate.<ref>{{cite book | veditors = Wolff JA | vauthors = Chang PL | date = 1994 | chapter = Calcium phosphate-mediated DNA transfection | pages = 157–179 | title = Gene Therapeutics | location = Boston | publisher = Birkhauser | isbn = 978-1-4684-6822-9 | doi = 10.1007/978-1-4684-6822-9_9 }}</ref> Further, after some time within the microcapsule, cells form clusters that inhibit the exchange of oxygen and metabolic waste,<ref>{{cite journal | vauthors = Ponce S, Orive G, Gascón AR, Hernández RM, Pedraz JL | title = Microcapsules prepared with different biomaterials to immobilize GDNF secreting 3T3 fibroblasts | journal = International Journal of Pharmaceutics | volume = 293 | issue = 1-2 | pages = 1–10 | date = April 2005 | pmid = 15778039 | doi = 10.1016/j.ijpharm.2004.10.028 }}</ref> leading to [[apoptosis]] and [[necrosis]] thus limiting the efficacy of the cells and activating the host's [[immune system]].
The most common method of preparation of artificial cells is through [[cell encapsulation]]. Encapsulated cells are typically achieved through the generation of controlled-size droplets from a liquid cell [[Suspension (chemistry)|suspension]] which are then rapidly solidified or gelated to provide added stability. The stabilization may be achieved through a change in temperature or via material crosslinking.<ref name=Prakash/> The microenvironment that a cell sees changes upon encapsulation. It typically goes from being on a [[monolayer]] to a suspension in a polymer scaffold within a polymeric membrane. A drawback of the technique is that encapsulating a cell decreases its viability and ability to proliferate and differentiate.<ref>{{cite book | veditors = Wolff JA | vauthors = Chang PL | date = 1994 | chapter = Calcium phosphate-mediated DNA transfection | pages = 157–179 | title = Gene Therapeutics | location = Boston | publisher = Birkhauser | isbn = 978-1-4684-6822-9 | doi = 10.1007/978-1-4684-6822-9_9 }}</ref> Further, after some time within the microcapsule, cells form clusters that inhibit the exchange of oxygen and metabolic waste,<ref>{{cite journal | vauthors = Ponce S, Orive G, Gascón AR, Hernández RM, Pedraz JL | title = Microcapsules prepared with different biomaterials to immobilize GDNF secreting 3T3 fibroblasts | journal = International Journal of Pharmaceutics | volume = 293 | issue = 1-2 | pages = 1–10 | date = April 2005 | pmid = 15778039 | doi = 10.1016/j.ijpharm.2004.10.028 }}</ref> leading to [[apoptosis]] and [[necrosis]] thus limiting the efficacy of the cells and activating the host's [[immune system]].
Artificial cells have been successful for transplanting a number of cells including islets of Langerhans for diabetes treatment, parathyroid cells and adrenal cortex cells.
Artificial cells have been successful for transplanting a number of cells including islets of Langerhans for diabetes treatment, parathyroid cells and adrenal cortex cells.
最常用的制备人工细胞的方法是细胞包裹。微囊细胞通常由液体细胞悬浮液中产生控制尺寸的液滴获取，然后快速凝固或凝胶化以提供额外的稳定性。稳定化可以通过温度的变化或材料的交联来实现。细胞的微环境在包裹后发生变化，且通常从单分子层到悬浮在聚合物膜内的聚合物支架上。这种技术的缺点是微囊细胞会降低其生存能力以及增殖和分化能力。此外，在微囊中待一段时间后，细胞会形成团簇，抑制氧气和代谢废物的交换，导致细胞凋亡和坏死，从而限制细胞的功效，激活宿主的免疫系统。人工细胞已经成功地移植了一些细胞，包括治疗糖尿病的胰岛、甲状旁腺细胞和肾上腺皮质细胞。
====Encapsulated hepatocytes====
====Encapsulated hepatocytes====
Shortage of organ donors make artificial cells key players in alternative therapies for [[liver failure]]. The use of artificial cells for [[hepatocyte]] transplantation has demonstrated feasibility and efficacy in providing liver function in models of animal liver disease and [[bioartificial liver devices]].<ref name=Dixit>{{cite journal | vauthors = Dixit V, Gitnick G | title = The bioartificial liver: state-of-the-art | journal = The European Journal of Surgery. Supplement. | volume = 164 | issue = 582 | pages = 71–76 | date = 27 November 2003 | pmid = 10029369 | doi = 10.1080/11024159850191481 | name-list-style = vanc }}</ref> Research stemmed off experiments in which the hepatocytes were attached to the surface of a micro-carriers<ref name="pmid2426782">{{cite journal | vauthors = Demetriou AA, Whiting JF, Feldman D, Levenson SM, Chowdhury NR, Moscioni AD, Kram M, Chowdhury JR | display-authors = 6 | title = Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes | journal = Science | volume = 233 | issue = 4769 | pages = 1190–1192 | date = September 1986 | pmid = 2426782 | doi = 10.1126/science.2426782 | bibcode = 1986Sci...233.1190D }}</ref> and has evolved into hepatocytes which are encapsulated in a three-dimensional matrix in [[alginate]] microdroplets covered by an outer skin of [[polylysine]]. A key advantage to this delivery method is the circumvention of [[immunosuppression]] therapy for the duration of the treatment. Hepatocyte encapsulations have been proposed for use in a [[bioartificial liver device|bioartifical liver]]. The device consists of a cylindrical chamber imbedded with isolated hepatocytes through which patient plasma is circulated extra-corporeally in a type of [[hemoperfusion]]. Because microcapsules have a high [[surface area]] to [[volume]] ratio, they provide large surface for substrate diffusion and can accommodate a large number of hepatocytes. Treatment to induced liver failure mice showed a significant increase in the rate of survival.<ref name= 'Dixit' /> Artificial liver systems are still in early development but show potential for patients waiting for [[organ transplant]] or while a patient's own liver regenerates sufficiently to resume normal function. So far, clinical trials using artificial liver systems and hepatocyte transplantation in end-stage liver diseases have shown improvement of health markers but have not yet improved survival.<ref>{{cite journal | vauthors = Sgroi A, Serre-Beinier V, Morel P, Bühler L | title = What clinical alternatives to whole liver transplantation? Current status of artificial devices and hepatocyte transplantation | journal = Transplantation | volume = 87 | issue = 4 | pages = 457–466 | date = February 2009 | pmid = 19307780 | doi = 10.1097/TP.0b013e3181963ad3 }}</ref> The short longevity and aggregation of artificial hepatocytes after transplantation are the main obstacles encountered.
微囊肝细胞
Shortage of organ donors make artificial cells key players in alternative therapies for [[liver failure]]. The use of artificial cells for [[hepatocyte]] transplantation has demonstrated feasibility and efficacy in providing liver function in models of animal liver disease and [[bioartificial liver devices]].<ref name="Dixit">{{cite journal | vauthors = Dixit V, Gitnick G | title = The bioartificial liver: state-of-the-art | journal = The European Journal of Surgery. Supplement. | volume = 164 | issue = 582 | pages = 71–76 | date = 27 November 2003 | pmid = 10029369 | doi = 10.1080/11024159850191481 | name-list-style = vanc }}</ref> Research stemmed off experiments in which the hepatocytes were attached to the surface of a micro-carriers<ref name="pmid2426782">{{cite journal | vauthors = Demetriou AA, Whiting JF, Feldman D, Levenson SM, Chowdhury NR, Moscioni AD, Kram M, Chowdhury JR | display-authors = 6 | title = Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes | journal = Science | volume = 233 | issue = 4769 | pages = 1190–1192 | date = September 1986 | pmid = 2426782 | doi = 10.1126/science.2426782 | bibcode = 1986Sci...233.1190D }}</ref> and has evolved into hepatocytes which are encapsulated in a three-dimensional matrix in [[alginate]] microdroplets covered by an outer skin of [[polylysine]]. A key advantage to this delivery method is the circumvention of [[immunosuppression]] therapy for the duration of the treatment. Hepatocyte encapsulations have been proposed for use in a [[bioartificial liver device|bioartifical liver]]. The device consists of a cylindrical chamber imbedded with isolated hepatocytes through which patient plasma is circulated extra-corporeally in a type of [[hemoperfusion]]. Because microcapsules have a high [[surface area]] to [[volume]] ratio, they provide large surface for substrate diffusion and can accommodate a large number of hepatocytes. Treatment to induced liver failure mice showed a significant increase in the rate of survival.<ref name="Dixit" /> Artificial liver systems are still in early development but show potential for patients waiting for [[organ transplant]] or while a patient's own liver regenerates sufficiently to resume normal function. So far, clinical trials using artificial liver systems and hepatocyte transplantation in end-stage liver diseases have shown improvement of health markers but have not yet improved survival.<ref>{{cite journal | vauthors = Sgroi A, Serre-Beinier V, Morel P, Bühler L | title = What clinical alternatives to whole liver transplantation? Current status of artificial devices and hepatocyte transplantation | journal = Transplantation | volume = 87 | issue = 4 | pages = 457–466 | date = February 2009 | pmid = 19307780 | doi = 10.1097/TP.0b013e3181963ad3 }}</ref> The short longevity and aggregation of artificial hepatocytes after transplantation are the main obstacles encountered.
Hepatocytes co-encapsulated with [[stem cells]] show greater viability in culture and after implantation<ref>{{cite journal | vauthors = Liu ZC, Chang TM | title = Increased viability of transplanted hepatocytes when hepatocytes are co-encapsulated with bone marrow stem cells using a novel method | journal = Artificial Cells, Blood Substitutes, and Immobilization Biotechnology | volume = 30 | issue = 2 | pages = 99–112 | date = March 2002 | pmid = 12027231 | doi = 10.1081/bio-120003191 | s2cid = 26667880 }}</ref> and implantation of artificial stem cells alone have also shown liver regeneration.<ref>{{cite book| veditors = Pedraz JL, Orive G |title=Therapeutic applications of cell microencapsulation|year=2010|publisher=Springer Science+Business Media|location=New York|isbn=978-1-4419-5785-6|edition=Online-Ausg.}}</ref> As such interest has arisen in the use of stem cells for encapsulation in [[regenerative medicine]].
Hepatocytes co-encapsulated with [[stem cells]] show greater viability in culture and after implantation<ref>{{cite journal | vauthors = Liu ZC, Chang TM | title = Increased viability of transplanted hepatocytes when hepatocytes are co-encapsulated with bone marrow stem cells using a novel method | journal = Artificial Cells, Blood Substitutes, and Immobilization Biotechnology | volume = 30 | issue = 2 | pages = 99–112 | date = March 2002 | pmid = 12027231 | doi = 10.1081/bio-120003191 | s2cid = 26667880 }}</ref> and implantation of artificial stem cells alone have also shown liver regeneration.<ref>{{cite book| veditors = Pedraz JL, Orive G |title=Therapeutic applications of cell microencapsulation|year=2010|publisher=Springer Science+Business Media|location=New York|isbn=978-1-4419-5785-6|edition=Online-Ausg.}}</ref> As such interest has arisen in the use of stem cells for encapsulation in [[regenerative medicine]].
Hepatocytes co-encapsulated with stem cells show greater viability in culture and after implantation and implantation of artificial stem cells alone have also shown liver regeneration. As such interest has arisen in the use of stem cells for encapsulation in regenerative medicine.
Hepatocytes co-encapsulated with stem cells show greater viability in culture and after implantation and implantation of artificial stem cells alone have also shown liver regeneration. As such interest has arisen in the use of stem cells for encapsulation in regenerative medicine.
器官捐献者的短缺使人工细胞成为治疗肝衰竭替代疗法的关键。人工细胞用于肝细胞移植已被证实在动物肝病模型和生物人工肝装置中提供肝功能的可行性和有效性。实验中，肝细胞附着在微载体表面，然后进化成包裹在由聚赖氨酸外皮覆盖的海藻酸钠微滴中的三维基质中的肝细胞。这种给药方法的一个关键优势是在治疗期间避免了免疫抑制治疗。微囊肝细胞已被提议用于生物人工肝。该装置由一个嵌有分离肝细胞的圆柱形腔室组成，病人的血浆通过这个腔室在一种血液灌流中循环。由于微囊具有很高的比表面积和体积比，它们为基质扩散提供了较大的表面积，并且可以容纳大量的肝细胞。对诱导性肝衰竭小鼠的治疗显示存活率显著提高。人工肝系统仍处于早期发展阶段，但对于等待器官移植或者病人自身的肝脏重新充分恢复正常功能的病人来说，显示出了潜力。迄今为止，应用人工肝系统和肝细胞移植治疗终末期肝病的临床试验表明，健康指标有所改善，但还没有提高存活率。移植后人工肝细胞的短寿命和聚集是目前肝移植面临的主要障碍。与干细胞一同包裹的肝细胞在培养和植入后显示出更高的存活率，单独植入人工干细胞也可以促成肝的再生。因此，在再生医学中利用干细胞封装的研究引起了人们的兴趣。
====Encapsulated bacterial cells====
====Encapsulated bacterial cells====
The oral ingestion of live bacterial cell [[Colony (biology)|colonies]] has been proposed and is currently in therapy for the modulation of intestinal [[Flora (microbiology)|microflora]],<ref>{{cite journal | vauthors = Mattila-Sandholm T, Blum S, Collins JK, Crittenden R, De Vos W, Dunne C, Fondén R, Grenov G, Isolauri E, Kiely B, Marteau P, Morelli L, Ouwehand A, Reniero R, Saarela M, Salminen S, Saxelin M, Schiffrin E, Shanahan F, Vaughan E, von Wright A | display-authors = 6 |title=Probiotics: towards demonstrating efficacy|journal=Trends in Food Science & Technology|date=1 December 1999 |volume=10|issue=12|pages=393–399|doi=10.1016/S0924-2244(00)00029-7 }}</ref> prevention of [[diarrheal diseases]],<ref>{{cite journal | vauthors = Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ | title = Efficacy of probiotic use in acute diarrhea in children: a meta-analysis | journal = Digestive Diseases and Sciences | volume = 47 | issue = 11 | pages = 2625–2634 | date = November 2002 | pmid = 12452406 | doi = 10.1023/A:1020501202369 | s2cid = 207559325 }}</ref> treatment of [[Helicobacter pylori|''H. Pylori'']] infections, atopic inflammations,<ref>{{cite journal | vauthors = Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S | title = Probiotics in the management of atopic eczema | journal = Clinical and Experimental Allergy | volume = 30 | issue = 11 | pages = 1604–1610 | date = November 2000 | pmid = 11069570 | doi = 10.1046/j.1365-2222.2000.00943.x | s2cid = 13524021 }}</ref> [[lactose intolerance]]<ref>{{cite journal | vauthors = Lin MY, Yen CL, Chen SH | title = Management of lactose maldigestion by consuming milk containing lactobacilli | journal = Digestive Diseases and Sciences | volume = 43 | issue = 1 | pages = 133–137 | date = January 1998 | pmid = 9508514 | doi = 10.1023/A:1018840507952 | s2cid = 22890925 }}</ref> and [[immune modulation]],<ref>{{cite journal| vauthors = Gill HS |title=Stimulation of the Immune System by Lactic Cultures|journal=International Dairy Journal|date=1 May 1998 |volume=8|issue=5–6|pages=535–544|doi=10.1016/S0958-6946(98)00074-0}}</ref> amongst others. The proposed mechanism of action is not fully understood but is believed to have two main effects. The first is the nutritional effect, in which the bacteria compete with toxin producing bacteria. The second is the sanitary effect, which stimulates resistance to colonization and stimulates [[immune response]].<ref name=Prakash/> The oral delivery of bacterial cultures is often a problem because they are targeted by the immune system and often destroyed when taken orally. Artificial cells help address these issues by providing mimicry into the body and selective or long term release thus increasing the viability of bacteria reaching the [[gastrointestinal system]].<ref name="Prakash">{{cite book| vauthors = Prakash S |title=Artificial cells, cell engineering and therapy.|year=2007|publisher=Woodhead Publishing Limited|location=Boca Raton, Fl|isbn=978-1-84569-036-6}}</ref> In addition, live bacterial cell encapsulation can be engineered to allow diffusion of small molecules including peptides into the body for therapeutic purposes.<ref name=Prakash/> Membranes that have proven successful for bacterial delivery include [[cellulose acetate]] and variants of [[alginate]].<ref name=Prakash/> Additional uses that have arosen from encapsulation of bacterial cells include protection against challenge from [[Mycobacterium tuberculosis|''M. Tuberculosis'']]<ref>{{cite journal | vauthors = Aldwell FE, Tucker IG, de Lisle GW, Buddle BM | title = Oral delivery of Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in mice | journal = Infection and Immunity | volume = 71 | issue = 1 | pages = 101–108 | date = January 2003 | pmid = 12496154 | pmc = 143408 | doi = 10.1128/IAI.71.1.101-108.2003 }}</ref> and upregulation of Ig secreting cells from the immune system.<ref>{{cite journal | vauthors = Park JH, Um JI, Lee BJ, Goh JS, Park SY, Kim WS, Kim PH | title = Encapsulated Bifidobacterium bifidum potentiates intestinal IgA production | journal = Cellular Immunology | volume = 219 | issue = 1 | pages = 22–27 | date = September 2002 | pmid = 12473264 | doi = 10.1016/S0008-8749(02)00579-8 }}</ref> The technology is limited by the risk of systemic infections, adverse metabolic activities and the risk of gene transfer.<ref name=Prakash/> However, the greater challenge remains the delivery of sufficient viable bacteria to the site of interest.<ref name=Prakash/>
微囊细菌细胞
The oral ingestion of live bacterial cell [[Colony (biology)|colonies]] has been proposed and is currently in therapy for the modulation of intestinal [[Flora (microbiology)|microflora]],<ref>{{cite journal | vauthors = Mattila-Sandholm T, Blum S, Collins JK, Crittenden R, De Vos W, Dunne C, Fondén R, Grenov G, Isolauri E, Kiely B, Marteau P, Morelli L, Ouwehand A, Reniero R, Saarela M, Salminen S, Saxelin M, Schiffrin E, Shanahan F, Vaughan E, von Wright A | display-authors = 6 |title=Probiotics: towards demonstrating efficacy|journal=Trends in Food Science & Technology|date=1 December 1999 |volume=10|issue=12|pages=393–399|doi=10.1016/S0924-2244(00)00029-7 }}</ref> prevention of [[diarrheal diseases]],<ref>{{cite journal | vauthors = Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ | title = Efficacy of probiotic use in acute diarrhea in children: a meta-analysis | journal = Digestive Diseases and Sciences | volume = 47 | issue = 11 | pages = 2625–2634 | date = November 2002 | pmid = 12452406 | doi = 10.1023/A:1020501202369 | s2cid = 207559325 }}</ref> treatment of [[Helicobacter pylori|''H. Pylori'']] infections, atopic inflammations,<ref>{{cite journal | vauthors = Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S | title = Probiotics in the management of atopic eczema | journal = Clinical and Experimental Allergy | volume = 30 | issue = 11 | pages = 1604–1610 | date = November 2000 | pmid = 11069570 | doi = 10.1046/j.1365-2222.2000.00943.x | s2cid = 13524021 }}</ref> [[lactose intolerance]]<ref>{{cite journal | vauthors = Lin MY, Yen CL, Chen SH | title = Management of lactose maldigestion by consuming milk containing lactobacilli | journal = Digestive Diseases and Sciences | volume = 43 | issue = 1 | pages = 133–137 | date = January 1998 | pmid = 9508514 | doi = 10.1023/A:1018840507952 | s2cid = 22890925 }}</ref> and [[immune modulation]],<ref>{{cite journal| vauthors = Gill HS |title=Stimulation of the Immune System by Lactic Cultures|journal=International Dairy Journal|date=1 May 1998 |volume=8|issue=5–6|pages=535–544|doi=10.1016/S0958-6946(98)00074-0}}</ref> amongst others. The proposed mechanism of action is not fully understood but is believed to have two main effects. The first is the nutritional effect, in which the bacteria compete with toxin producing bacteria. The second is the sanitary effect, which stimulates resistance to colonization and stimulates [[immune response]].<ref name="Prakash" /> The oral delivery of bacterial cultures is often a problem because they are targeted by the immune system and often destroyed when taken orally. Artificial cells help address these issues by providing mimicry into the body and selective or long term release thus increasing the viability of bacteria reaching the [[gastrointestinal system]].<ref name="Prakash">{{cite book| vauthors = Prakash S |title=Artificial cells, cell engineering and therapy.|year=2007|publisher=Woodhead Publishing Limited|location=Boca Raton, Fl|isbn=978-1-84569-036-6}}</ref> In addition, live bacterial cell encapsulation can be engineered to allow diffusion of small molecules including peptides into the body for therapeutic purposes.<ref name="Prakash" /> Membranes that have proven successful for bacterial delivery include [[cellulose acetate]] and variants of [[alginate]].<ref name="Prakash" /> Additional uses that have arosen from encapsulation of bacterial cells include protection against challenge from [[Mycobacterium tuberculosis|''M. Tuberculosis'']]<ref>{{cite journal | vauthors = Aldwell FE, Tucker IG, de Lisle GW, Buddle BM | title = Oral delivery of Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in mice | journal = Infection and Immunity | volume = 71 | issue = 1 | pages = 101–108 | date = January 2003 | pmid = 12496154 | pmc = 143408 | doi = 10.1128/IAI.71.1.101-108.2003 }}</ref> and upregulation of Ig secreting cells from the immune system.<ref>{{cite journal | vauthors = Park JH, Um JI, Lee BJ, Goh JS, Park SY, Kim WS, Kim PH | title = Encapsulated Bifidobacterium bifidum potentiates intestinal IgA production | journal = Cellular Immunology | volume = 219 | issue = 1 | pages = 22–27 | date = September 2002 | pmid = 12473264 | doi = 10.1016/S0008-8749(02)00579-8 }}</ref> The technology is limited by the risk of systemic infections, adverse metabolic activities and the risk of gene transfer.<ref name="Prakash" /> However, the greater challenge remains the delivery of sufficient viable bacteria to the site of interest.<ref name="Prakash" />
The oral ingestion of live bacterial cell colonies has been proposed and is currently in therapy for the modulation of intestinal microflora, prevention of diarrheal diseases, treatment of H. Pylori infections, atopic inflammations, lactose intolerance and immune modulation, amongst others. The proposed mechanism of action is not fully understood but is believed to have two main effects. The first is the nutritional effect, in which the bacteria compete with toxin producing bacteria. The second is the sanitary effect, which stimulates resistance to colonization and stimulates immune response. The oral delivery of bacterial cultures is often a problem because they are targeted by the immune system and often destroyed when taken orally. Artificial cells help address these issues by providing mimicry into the body and selective or long term release thus increasing the viability of bacteria reaching the gastrointestinal system. In addition, live bacterial cell encapsulation can be engineered to allow diffusion of small molecules including peptides into the body for therapeutic purposes. Membranes that have proven successful for bacterial delivery include cellulose acetate and variants of alginate. Additional uses that have arosen from encapsulation of bacterial cells include protection against challenge from M. Tuberculosis and upregulation of Ig secreting cells from the immune system. The technology is limited by the risk of systemic infections, adverse metabolic activities and the risk of gene transfer. However, the greater challenge remains the delivery of sufficient viable bacteria to the site of interest.
The oral ingestion of live bacterial cell colonies has been proposed and is currently in therapy for the modulation of intestinal microflora, prevention of diarrheal diseases, treatment of H. Pylori infections, atopic inflammations, lactose intolerance and immune modulation, amongst others. The proposed mechanism of action is not fully understood but is believed to have two main effects. The first is the nutritional effect, in which the bacteria compete with toxin producing bacteria. The second is the sanitary effect, which stimulates resistance to colonization and stimulates immune response. The oral delivery of bacterial cultures is often a problem because they are targeted by the immune system and often destroyed when taken orally. Artificial cells help address these issues by providing mimicry into the body and selective or long term release thus increasing the viability of bacteria reaching the gastrointestinal system. In addition, live bacterial cell encapsulation can be engineered to allow diffusion of small molecules including peptides into the body for therapeutic purposes. Membranes that have proven successful for bacterial delivery include cellulose acetate and variants of alginate. Additional uses that have arosen from encapsulation of bacterial cells include protection against challenge from M. Tuberculosis and upregulation of Ig secreting cells from the immune system. The technology is limited by the risk of systemic infections, adverse metabolic activities and the risk of gene transfer. However, the greater challenge remains the delivery of sufficient viable bacteria to the site of interest.
口服活菌群，目前正用于治疗调节肠道菌群，预防腹泻疾病，治疗幽门螺杆菌感染，特应性炎症，乳糖不耐受和免疫调节等症病。虽然其作用机制尚未得到充分理解，但被认为其具有两个主要作用。首先是营养效应，即细菌与产毒细菌竞争。第二是卫生效应，即刺激抵抗定殖和免疫反应。由于细菌培养物往往是免疫系统的目标，通常会在口服时被破坏，口服给药的方式便成了困难。人工细胞通过向体内提供拟态，以及其可选择的或长期的释放，来提高进入胃肠道系统的细菌的生存能力，从而帮助解决这些问题。此外，还可以设计活细菌包囊，使小分子(包括多肽)扩散到体内，以用于治疗。醋酸纤维素和海藻酸盐的变体等已被证明，可以成功用于细菌传递的膜。微囊细菌细胞的其他用途还包括保护细菌细胞免受结核分枝杆菌的攻击，以及促进免疫系统产生Ig分泌细胞。该技术受到系统性感染、不良代谢活动和基因转移风险的限制。然而，更大的挑战仍然是如何将足够多的有生命的细菌运送到目标部位。
====Artificial blood cells as oxygen carriers====
====Artificial blood cells as oxygen carriers====
{{main|Blood substitute}}
人工血细胞作为氧载体{{main|Blood substitute}}
Nano sized oxygen carriers are used as a type of [[red blood cell]] substitutes, although they lack other components of red blood cells. They are composed of a synthetic [[polymersome]] or an artificial membrane surrounding purified animal, human or recombinant [[hemoglobin]].<ref>{{cite journal | vauthors = Kim HW, Greenburg AG | title = Artificial oxygen carriers as red blood cell substitutes: a selected review and current status | journal = Artificial Organs | volume = 28 | issue = 9 | pages = 813–828 | date = September 2004 | pmid = 15320945 | doi = 10.1111/j.1525-1594.2004.07345.x }}</ref>
Nano sized oxygen carriers are used as a type of [[red blood cell]] substitutes, although they lack other components of red blood cells. They are composed of a synthetic [[polymersome]] or an artificial membrane surrounding purified animal, human or recombinant [[hemoglobin]].<ref>{{cite journal | vauthors = Kim HW, Greenburg AG | title = Artificial oxygen carriers as red blood cell substitutes: a selected review and current status | journal = Artificial Organs | volume = 28 | issue = 9 | pages = 813–828 | date = September 2004 | pmid = 15320945 | doi = 10.1111/j.1525-1594.2004.07345.x }}</ref>
Overall, hemoglobin delivery continues to be a challenge because it is highly toxic when delivered without any modifications. In some clinical trials, vasopressor effects have been observed.<ref>{{cite book | vauthors = Nelson DJ | date = 1998 | chapter = Blood and HemAssistTM (DCLHb): Potentially a complementary therapeutic team | title = Blood Substitutes: Principles, Methods, Products and Clinical Trials | veditors = Chang TM | volume = 2 | publisher = Karger | location = Basel | pages = 39–57 }}</ref><ref>{{cite journal | vauthors = Burhop KE, Estep TE | date = 2001 | title = Hemoglobin induced myocardial lesions | journal = Artificial Cells, Blood Substitutes, and Biotechnology | volume = 29 | issue = 2 | pages = 101–106 | doi = 10.1080/10731190108951271 | pmc = 3555357 }}</ref>
Overall, hemoglobin delivery continues to be a challenge because it is highly toxic when delivered without any modifications. In some clinical trials, vasopressor effects have been observed.<ref>{{cite book | vauthors = Nelson DJ | date = 1998 | chapter = Blood and HemAssistTM (DCLHb): Potentially a complementary therapeutic team | title = Blood Substitutes: Principles, Methods, Products and Clinical Trials | veditors = Chang TM | volume = 2 | publisher = Karger | location = Basel | pages = 39–57 }}</ref><ref>{{cite journal | vauthors = Burhop KE, Estep TE | date = 2001 | title = Hemoglobin induced myocardial lesions | journal = Artificial Cells, Blood Substitutes, and Biotechnology | volume = 29 | issue = 2 | pages = 101–106 | doi = 10.1080/10731190108951271 | pmc = 3555357 }}</ref>
Overall, hemoglobin delivery continues to be a challenge because it is highly toxic when delivered without any modifications. In some clinical trials, vasopressor effects have been observed.
Overall, hemoglobin delivery continues to be a challenge because it is highly toxic when delivered without any modifications. In some clinical trials, vasopressor effects have been observed.
人工血细胞作为氧载体被用作一种红细胞替代品，尽管它们缺乏红细胞的其他成分。它们由一种合成的聚合体或围绕着纯化的动物、人或重组的血红蛋白的人工膜组成。总的来说，血红蛋白的输送仍然是一个挑战，因为它在没有任何修饰的情况下输送时是剧毒的。在一些临床试验中，人们观察到血管升压效应。
====Artificial red blood cells====
====Artificial red blood cells====
{{main|Respirocyte}}
人工红细胞{{main|Respirocyte}}
Research interest in the use of artificial cells for blood arose after the [[AIDS]] scare of the 1980s. Besides bypassing the potential for disease transmission, artificial red blood cells are desired because they eliminate drawbacks associated with allogenic blood transfusions such as blood typing, immune reactions and its short storage life of 42 days. A [[hemoglobin]] substitute may be stored at room temperature and not under refrigeration for more than a year.<ref name= 'Chang 2007' /> Attempts have been made to develop a complete working red blood cell which comprises carbonic not only an oxygen carrier but also the enzymes associated with the cell. The first attempt was made in 1957 by replacing the red blood cell membrane by an ultrathin polymeric membrane<ref>{{cite journal|title=30th Anniversary in Artificial Red Blood Cell Research|journal=Artificial Cells, Blood Substitutes and Biotechnology|date=1 January 1988 |volume=16|issue=1–3|pages=1–9|doi=10.3109/10731198809132551}}</ref> which was followed by encapsulation through a [[lipid membrane]]<ref>{{cite journal | vauthors = Djordjevich L, Miller IF | title = Synthetic erythrocytes from lipid encapsulated hemoglobin | journal = Experimental Hematology | volume = 8 | issue = 5 | pages = 584–592 | date = May 1980 | pmid = 7461058 }}</ref> and more recently a biodegradable polymeric membrane.<ref name= 'Chang 2007' />
Research interest in the use of artificial cells for blood arose after the [[AIDS]] scare of the 1980s. Besides bypassing the potential for disease transmission, artificial red blood cells are desired because they eliminate drawbacks associated with allogenic blood transfusions such as blood typing, immune reactions and its short storage life of 42 days. A [[hemoglobin]] substitute may be stored at room temperature and not under refrigeration for more than a year.<ref name= 'Chang 2007' /> Attempts have been made to develop a complete working red blood cell which comprises carbonic not only an oxygen carrier but also the enzymes associated with the cell. The first attempt was made in 1957 by replacing the red blood cell membrane by an ultrathin polymeric membrane<ref>{{cite journal|title=30th Anniversary in Artificial Red Blood Cell Research|journal=Artificial Cells, Blood Substitutes and Biotechnology|date=1 January 1988 |volume=16|issue=1–3|pages=1–9|doi=10.3109/10731198809132551}}</ref> which was followed by encapsulation through a [[lipid membrane]]<ref>{{cite journal | vauthors = Djordjevich L, Miller IF | title = Synthetic erythrocytes from lipid encapsulated hemoglobin | journal = Experimental Hematology | volume = 8 | issue = 5 | pages = 584–592 | date = May 1980 | pmid = 7461058 }}</ref> and more recently a biodegradable polymeric membrane.<ref name= 'Chang 2007' />
A biological red blood cell membrane including [[lipids]] and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing [[macrophage]] uptake and systemic clearance.<ref>{{cite journal | vauthors = Hu CM, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L | title = Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 27 | pages = 10980–10985 | date = July 2011 | pmid = 21690347 | pmc = 3131364 | doi = 10.1073/pnas.1106634108 | doi-access = free | bibcode = 2011PNAS..10810980H }}</ref>
A biological red blood cell membrane including [[lipids]] and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing [[macrophage]] uptake and systemic clearance.<ref>{{cite journal | vauthors = Hu CM, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L | title = Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 27 | pages = 10980–10985 | date = July 2011 | pmid = 21690347 | pmc = 3131364 | doi = 10.1073/pnas.1106634108 | doi-access = free | bibcode = 2011PNAS..10810980H }}</ref>
A biological red blood cell membrane including lipids and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing macrophage uptake and systemic clearance.
A biological red blood cell membrane including lipids and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing macrophage uptake and systemic clearance.
在1980年代的艾滋病恐慌之后，人们对使用人工红细胞制造血液产生了研究兴趣。除了避开疾病传播的可能性之外，人工红细胞也是人们所需要的，因为它们可以消除与同种异体输血相关的缺点，如血型鉴定、免疫反应及其短暂的42天储存期。血红蛋白替代物可以存放在室温下，而不是在冷藏条件下存放一年以上。人们已经尝试开发出一种完整工作的红细胞，它不仅包含碳酸，而且包含氧载体和与细胞相关的酶。第一次尝试是在1957年，用超薄聚合物膜代替红细胞膜，然后通过脂质膜和最近的可生物降解聚合物膜进行包封。包括脂类和相关蛋白在内的生物红细胞膜还可以通过绕过巨噬细胞摄取和系统清除来包裹纳米颗粒和增加体内滞留时间。
====Artificial leuko-polymersomes ====
====Artificial leuko-polymersomes ====
人工白细胞聚合体
A leuko-polymersome is a [[polymersome]] engineered to have the adhesive properties of a [[leukocyte]].<ref>{{cite journal | vauthors = Hammer DA, Robbins GP, Haun JB, Lin JJ, Qi W, Smith LA, Ghoroghchian PP, Therien MJ, Bates FS | display-authors = 6 | title = Leuko-polymersomes | journal = Faraday Discussions | volume = 139 | pages = 129–41; discussion 213–28, 419–20 | date = 1 January 2008 | pmid = 19048993 | pmc = 2714229 | doi = 10.1039/B717821B | bibcode = 2008FaDi..139..129H }}</ref> Polymersomes are vesicles composed of a bilayer sheet that can encapsulate many active molecules such as drugs or [[enzymes]]. By adding the adhesive properties of a leukocyte to their membranes, they can be made to slow down, or roll along epithelial walls within the quickly flowing [[circulatory system]].
A leuko-polymersome is a [[polymersome]] engineered to have the adhesive properties of a [[leukocyte]].<ref>{{cite journal | vauthors = Hammer DA, Robbins GP, Haun JB, Lin JJ, Qi W, Smith LA, Ghoroghchian PP, Therien MJ, Bates FS | display-authors = 6 | title = Leuko-polymersomes | journal = Faraday Discussions | volume = 139 | pages = 129–41; discussion 213–28, 419–20 | date = 1 January 2008 | pmid = 19048993 | pmc = 2714229 | doi = 10.1039/B717821B | bibcode = 2008FaDi..139..129H }}</ref> Polymersomes are vesicles composed of a bilayer sheet that can encapsulate many active molecules such as drugs or [[enzymes]]. By adding the adhesive properties of a leukocyte to their membranes, they can be made to slow down, or roll along epithelial walls within the quickly flowing [[circulatory system]].
A leuko-polymersome is a polymersome engineered to have the adhesive properties of a leukocyte. Polymersomes are vesicles composed of a bilayer sheet that can encapsulate many active molecules such as drugs or enzymes. By adding the adhesive properties of a leukocyte to their membranes, they can be made to slow down, or roll along epithelial walls within the quickly flowing circulatory system.
A leuko-polymersome is a polymersome engineered to have the adhesive properties of a leukocyte. Polymersomes are vesicles composed of a bilayer sheet that can encapsulate many active molecules such as drugs or enzymes. By adding the adhesive properties of a leukocyte to their membranes, they can be made to slow down, or roll along epithelial walls within the quickly flowing circulatory system.
人工白细胞聚合体是一种具有白细胞粘附特性的高分子囊泡。高分子囊泡是由双层薄片组成的囊泡，可以包裹许多活性分子，如药物或酶。通过将白细胞的粘附特性添加到细胞膜上，白细胞可以减慢速度，或者在快速流动的循环系统内沿着上皮细胞壁滚动。
==Unconventional types of artificial cells==
==Unconventional types of artificial cells==
非常规类型的人工细胞
===Electronic artificial cell===
===Electronic artificial cell===
The concept of an Electronic Artificial Cell has been expanded in a series of 3 EU projects coordinated by John McCaskill from 2004 to 2015.
The concept of an Electronic Artificial Cell has been expanded in a series of 3 EU projects coordinated by John McCaskill from 2004 to 2015.
The concept of an Electronic Artificial Cell has been expanded in a series of 3 EU projects coordinated by John McCaskill from 2004 to 2015.
The concept of an Electronic Artificial Cell has been expanded in a series of 3 EU projects coordinated by John McCaskill from 2004 to 2015.
电子人工细胞的概念在2004年至2015年由约翰 · 麦卡斯基尔协调的一系列欧盟项目中得到扩展。
The [[European Commission]] sponsored the development of the Programmable Artificial Cell Evolution (PACE) program<ref name = "PACE">{{cite web | title = Programmable Artificial Cell Evolution" (PACE) | url = http://www.istpace.org/Web_Final_Report/the_pace_report/index.html?View=default | publisher = PACE Consortium }}</ref> from 2004 to 2008 whose goal was to lay the foundation for the creation of "microscopic self-organizing, self-replicating, and evolvable autonomous entities built from simple organic and inorganic substances that can be genetically programmed to perform specific functions"<ref name = "PACE" /> for the eventual integration into information systems. The PACE project developed the first Omega Machine, a microfluidic life support system for artificial cells that could complement chemically missing functionalities (as originally proposed by Norman Packard, Steen Rasmussen, Mark Beadau and John McCaskill). The ultimate aim was to attain an evolvable hybrid cell in a complex microscale programmable environment. The functions of the Omega Machine could then be removed stepwise, posing a series of solvable evolution challenges to the artificial cell chemistry. The project achieved chemical integration up to the level of pairs of the three core functions of artificial cells (a genetic subsystem, a containment system and a metabolic system), and generated novel spatially resolved programmable microfluidic environments for the integration of containment and genetic amplification.<ref name = "PACE" /> The project led to the creation of the European center for living technology.<ref>{{cite web | title = European center for living technology | url = http://www.ecltech.org/ecltech_j/ | archive-url = https://web.archive.org/web/20111214010917/http://www.ecltech.org/ecltech_j/ | url-status = dead | archive-date = 2011-12-14 | publisher = European Center for Living Technology }}</ref>
The [[European Commission]] sponsored the development of the Programmable Artificial Cell Evolution (PACE) program<ref name = "PACE">{{cite web | title = Programmable Artificial Cell Evolution" (PACE) | url = http://www.istpace.org/Web_Final_Report/the_pace_report/index.html?View=default | publisher = PACE Consortium }}</ref> from 2004 to 2008 whose goal was to lay the foundation for the creation of "microscopic self-organizing, self-replicating, and evolvable autonomous entities built from simple organic and inorganic substances that can be genetically programmed to perform specific functions"<ref name = "PACE" /> for the eventual integration into information systems. The PACE project developed the first Omega Machine, a microfluidic life support system for artificial cells that could complement chemically missing functionalities (as originally proposed by Norman Packard, Steen Rasmussen, Mark Beadau and John McCaskill). The ultimate aim was to attain an evolvable hybrid cell in a complex microscale programmable environment. The functions of the Omega Machine could then be removed stepwise, posing a series of solvable evolution challenges to the artificial cell chemistry. The project achieved chemical integration up to the level of pairs of the three core functions of artificial cells (a genetic subsystem, a containment system and a metabolic system), and generated novel spatially resolved programmable microfluidic environments for the integration of containment and genetic amplification.<ref name = "PACE" /> The project led to the creation of the European center for living technology.<ref>{{cite web | title = European center for living technology | url = http://www.ecltech.org/ecltech_j/ | archive-url = https://web.archive.org/web/20111214010917/http://www.ecltech.org/ecltech_j/ | url-status = dead | archive-date = 2011-12-14 | publisher = European Center for Living Technology }}</ref>
The European Commission sponsored the development of the Programmable Artificial Cell Evolution (PACE) program from 2004 to 2008 whose goal was to lay the foundation for the creation of "microscopic self-organizing, self-replicating, and evolvable autonomous entities built from simple organic and inorganic substances that can be genetically programmed to perform specific functions" for the eventual integration into information systems. The PACE project developed the first Omega Machine, a microfluidic life support system for artificial cells that could complement chemically missing functionalities (as originally proposed by Norman Packard, Steen Rasmussen, Mark Beadau and John McCaskill). The ultimate aim was to attain an evolvable hybrid cell in a complex microscale programmable environment. The functions of the Omega Machine could then be removed stepwise, posing a series of solvable evolution challenges to the artificial cell chemistry. The project achieved chemical integration up to the level of pairs of the three core functions of artificial cells (a genetic subsystem, a containment system and a metabolic system), and generated novel spatially resolved programmable microfluidic environments for the integration of containment and genetic amplification. The project led to the creation of the European center for living technology.
The European Commission sponsored the development of the Programmable Artificial Cell Evolution (PACE) program from 2004 to 2008 whose goal was to lay the foundation for the creation of "microscopic self-organizing, self-replicating, and evolvable autonomous entities built from simple organic and inorganic substances that can be genetically programmed to perform specific functions" for the eventual integration into information systems. The PACE project developed the first Omega Machine, a microfluidic life support system for artificial cells that could complement chemically missing functionalities (as originally proposed by Norman Packard, Steen Rasmussen, Mark Beadau and John McCaskill). The ultimate aim was to attain an evolvable hybrid cell in a complex microscale programmable environment. The functions of the Omega Machine could then be removed stepwise, posing a series of solvable evolution challenges to the artificial cell chemistry. The project achieved chemical integration up to the level of pairs of the three core functions of artificial cells (a genetic subsystem, a containment system and a metabolic system), and generated novel spatially resolved programmable microfluidic environments for the integration of containment and genetic amplification. The project led to the creation of the European center for living technology.
2004年至2008年，欧洲联盟委员会赞助制定了可编程人工细胞进化方案，其目标是为最终融入信息系统奠定基础，创建”由简单的有机和无机物质构成的微观自组织、自我复制和可进化的自主实体，这些物质可通过遗传程序进行编程，以履行特定功能”。PACE 项目开发了第一台欧米茄机器，这是一种人工细胞的微流体生命支持系统，可以补充化学缺失的功能(最初由诺曼 · 帕卡德、斯蒂恩 · 拉斯穆森、马克 · 比多和约翰 · 麦卡斯基尔提出)。最终目标是在复杂的微型可编程环境中实现可进化的混合细胞。欧米茄机器的功能可以逐步被移除，这对人工细胞化学提出了一系列可解决的进化挑战。该项目实现了人工细胞三个核心功能(遗传子系统、包容系统和新陈代谢系统)成对的化学整合，并为包容和基因扩增的整合创造了新的空间分辨可编程微流体环境。这个项目导致了欧洲生物技术中心的建立。
Following this research, in 2007, John McCaskill proposed to concentrate on an electronically complemented artificial cell, called the Electronic Chemical Cell. The key idea was to use a massively parallel array of electrodes coupled to locally dedicated electronic circuitry, in a two-dimensional thin film, to complement emerging chemical cellular functionality. Local electronic information defining the electrode switching and sensing circuits could serve as an electronic genome, complementing the molecular sequential information in the emerging protocols. A research proposal was successful with the [[European Commission]] and an international team of scientists partially overlapping with the PACE consortium commenced work 2008-2012 on the project Electronic Chemical Cells. The project demonstrated among other things that electronically controlled local transport of specific sequences could be used as an artificial spatial control system for the genetic proliferation of future artificial cells, and that core processes of metabolism could be delivered by suitably coated electrode arrays.
Following this research, in 2007, John McCaskill proposed to concentrate on an electronically complemented artificial cell, called the Electronic Chemical Cell. The key idea was to use a massively parallel array of electrodes coupled to locally dedicated electronic circuitry, in a two-dimensional thin film, to complement emerging chemical cellular functionality. Local electronic information defining the electrode switching and sensing circuits could serve as an electronic genome, complementing the molecular sequential information in the emerging protocols. A research proposal was successful with the [[European Commission]] and an international team of scientists partially overlapping with the PACE consortium commenced work 2008-2012 on the project Electronic Chemical Cells. The project demonstrated among other things that electronically controlled local transport of specific sequences could be used as an artificial spatial control system for the genetic proliferation of future artificial cells, and that core processes of metabolism could be delivered by suitably coated electrode arrays.
The major limitation of this approach, apart from the initial difficulties in mastering microscale electrochemistry and electrokinetics, is that the electronic system is interconnected as a rigid non-autonomous piece of macroscopic hardware. In 2011, McCaskill proposed to invert the geometry of electronics and chemistry : instead of placing chemicals in an active electronic medium, to place microscopic autonomous electronics in a chemical medium. He organized a project to tackle a third generation of Electronic Artificial Cells at the 100 µm scale that could self-assemble from two half-cells "lablets" to enclose an internal chemical space, and function with the aid of active electronics powered by the medium they are immersed in. Such cells can copy both their electronic and chemical contents and will be capable of evolution within the constraints provided by their special pre-synthesized microscopic building blocks. In September 2012 work commenced on this project.
The major limitation of this approach, apart from the initial difficulties in mastering microscale electrochemistry and electrokinetics, is that the electronic system is interconnected as a rigid non-autonomous piece of macroscopic hardware. In 2011, McCaskill proposed to invert the geometry of electronics and chemistry : instead of placing chemicals in an active electronic medium, to place microscopic autonomous electronics in a chemical medium. He organized a project to tackle a third generation of Electronic Artificial Cells at the 100 µm scale that could self-assemble from two half-cells "lablets" to enclose an internal chemical space, and function with the aid of active electronics powered by the medium they are immersed in. Such cells can copy both their electronic and chemical contents and will be capable of evolution within the constraints provided by their special pre-synthesized microscopic building blocks. In September 2012 work commenced on this project.
这种方法的主要局限性，除了最初在掌握微观电化学和电动力学方面的困难之外，是把电子系统作为一种刚性的、非自主的宏观硬件连接在一起。2011年，麦卡斯基尔提议颠倒电子学和化学的几何学: 不把化学物质放在活跃的电子介质中，而是把微观的自主电子学放在化学介质中。他组织了一个项目，以解决第三代100微米规模的电子人工细胞问题，这种细胞可以由两个半细胞”实验室”自我组装，以封闭内部化学空间，并借助浸入其中的有源电子设备发挥功能。这些细胞可以复制它们的电子和化学成分，并且能够在它们特殊的预合成微观构件所提供的约束条件下进化。2012年9月，这个项目开始了工作。
===Jeewanu===
===Jeewanu===
{{main|Jeewanu}}
杰瓦努{{main|Jeewanu}}
[[Jeewanu]] protocells are synthetic chemical particles that possess [[Cell membrane|cell]]-like structure and seem to have some functional living properties.<ref name="Grote 2011">{{cite journal | vauthors = Grote M | title = Jeewanu, or the 'particles of life'. The approach of Krishna Bahadur in 20th century origin of life research | journal = Journal of Biosciences | volume = 36 | issue = 4 | pages = 563–570 | date = September 2011 | pmid = 21857103 | doi = 10.1007/s12038-011-9087-0 | url = http://www.ias.ac.in/jbiosci/grote_3677.pdf | url-status = dead | s2cid = 19551399 | archive-url = https://web.archive.org/web/20140323225723/http://www.ias.ac.in/jbiosci/grote_3677.pdf | archive-date = 2014-03-23 }}</ref> First synthesized in 1963 from simple minerals and basic organics while exposed to [[sunlight]], it is still reported to have some metabolic capabilities, the presence of [[semipermeable membrane]], [[amino acids]], [[phospholipids]], [[carbohydrates]] and RNA-like molecules.<ref name="Grote 2011" /><ref name="Gupta 2013">{{cite journal |title=Histochemical localisation of RNA-like material in photochemically formed self-sustaining, abiogenic supramolecular assemblies 'Jeewanu' |journal=Int. Res. J. Of Science & Engineering |date=2013 | vauthors = Gupta VK, Rai RK |volume=1 |issue=1 |pages=1–4 |issn=2322-0015 }}</ref> However, the nature and properties of the Jeewanu remains to be clarified.<ref name="Grote 2011" /><ref name="Gupta 2013" /><ref name="NASA 1967">{{cite journal |first1=Linda D. |last1=Caren |first2=Cyril |last2=Ponnamperuma |year=1967 |url=https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19670026284.pdf |title=A review of some experiments on the synthesis of 'Jeewanu' |journal=NASA Technical Memorandum X-1439 }}</ref>
[[Jeewanu]] protocells are synthetic chemical particles that possess [[Cell membrane|cell]]-like structure and seem to have some functional living properties.<ref name="Grote 2011">{{cite journal | vauthors = Grote M | title = Jeewanu, or the 'particles of life'. The approach of Krishna Bahadur in 20th century origin of life research | journal = Journal of Biosciences | volume = 36 | issue = 4 | pages = 563–570 | date = September 2011 | pmid = 21857103 | doi = 10.1007/s12038-011-9087-0 | url = http://www.ias.ac.in/jbiosci/grote_3677.pdf | url-status = dead | s2cid = 19551399 | archive-url = https://web.archive.org/web/20140323225723/http://www.ias.ac.in/jbiosci/grote_3677.pdf | archive-date = 2014-03-23 }}</ref> First synthesized in 1963 from simple minerals and basic organics while exposed to [[sunlight]], it is still reported to have some metabolic capabilities, the presence of [[semipermeable membrane]], [[amino acids]], [[phospholipids]], [[carbohydrates]] and RNA-like molecules.<ref name="Grote 2011" /><ref name="Gupta 2013">{{cite journal |title=Histochemical localisation of RNA-like material in photochemically formed self-sustaining, abiogenic supramolecular assemblies 'Jeewanu' |journal=Int. Res. J. Of Science & Engineering |date=2013 | vauthors = Gupta VK, Rai RK |volume=1 |issue=1 |pages=1–4 |issn=2322-0015 }}</ref> However, the nature and properties of the Jeewanu remains to be clarified.<ref name="Grote 2011" /><ref name="Gupta 2013" /><ref name="NASA 1967">{{cite journal |first1=Linda D. |last1=Caren |first2=Cyril |last2=Ponnamperuma |year=1967 |url=https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19670026284.pdf |title=A review of some experiments on the synthesis of 'Jeewanu' |journal=NASA Technical Memorandum X-1439 }}</ref>
Jeewanu protocells are synthetic chemical particles that possess cell-like structure and seem to have some functional living properties. First synthesized in 1963 from simple minerals and basic organics while exposed to sunlight, it is still reported to have some metabolic capabilities, the presence of semipermeable membrane, amino acids, phospholipids, carbohydrates and RNA-like molecules. However, the nature and properties of the Jeewanu remains to be clarified.
Jeewanu protocells are synthetic chemical particles that possess cell-like structure and seem to have some functional living properties. First synthesized in 1963 from simple minerals and basic organics while exposed to sunlight, it is still reported to have some metabolic capabilities, the presence of semipermeable membrane, amino acids, phospholipids, carbohydrates and RNA-like molecules. However, the nature and properties of the Jeewanu remains to be clarified.
杰瓦努原始细胞是具有细胞样结构的合成化学粒子，似乎具有一定的功能活性。1963年首次在阳光下由简单矿物质和基本有机物合成，据报道它仍然具有一些新陈代谢能力，包括半透膜、氨基酸、磷脂、碳水化合物和类 RNA分子。然而，杰瓦努的性质和属性仍有待澄清。
== See also ==
== See also ==
* [[Protocell]]
* [[Protocell]]
* [[Synthetic biology]]
* [[Synthetic biology]]
* [[Artificial life]]
* [[Artificial life]]
* [[Targeted drug delivery]]
* [[Targeted drug delivery]]
* [[Respirocyte]]
* [[Respirocyte]]
* [[Chemoton]]
* [[Chemoton]]
* [[Jeewanu]]
* [[Jeewanu]]
* [[Build-a-Cell]]
* [[Build-a-Cell]]
* Protocell 原始细胞
* Synthetic biology 合成生物学
* Artificial life 人造生命
* Targeted drug delivery 靶向给药
* Respirocyte 呼吸细胞
* Chemoton 化学药品
* Jeewanu 杰瓦努
* Build-a-Cell 建立一个细胞
== References ==
== References ==