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人工细胞 (查看源代码)

2022年3月20日 (日) 19:09的版本

删除460字节 、 2022年3月20日 (日) 19:09
无编辑摘要
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自下而上构建人工细胞的方法涉及创建一个完全由非生物材料构成的原生质体。正如术语“细胞”所暗示的那样，一个前提是要生成某种定义了单个细胞单元的隔室。由于磷脂膜在所有活的生物细胞中起着选择性屏障的作用，<ref>{{cite journal | vauthors = Kamiya K, Takeuchi S | title = Giant liposome formation toward the synthesis of well-defined artificial cells | journal = Journal of Materials Chemistry B | volume = 5 | issue = 30 | pages = 5911–5923 | date = August 2017 | pmid = 32264347 | doi = 10.1039/C7TB01322A }}</ref> 因此可以选择磷脂膜作为一个明显的划分界限。科学家通过将生物分子包裹在细胞大小的磷脂小泡中，观察这些分子在生物细胞中的类似作用，从而重建某些细胞功能。<ref>{{cite journal | vauthors = Litschel T, Schwille P | title = Protein Reconstitution Inside Giant Unilamellar Vesicles | journal = Annual Review of Biophysics | volume = 50 | pages = 525–548 | date = May 2021 | pmid = 33667121 | doi = 10.1146/annurev-biophys-100620-114132 | s2cid = 232131463 }}</ref>类似地，功能性生物构建模块可以被封装在这些脂质隔室中，以实现人工细胞的合成(无论多么初级)。
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自下而上构建人工细胞的方法涉及创建一个完全由非生物材料构成的原生质体。正如术语“细胞”所暗示的那样，一个前提是要生成某种定义了单个细胞单元的隔室。由于磷脂膜在所有活的生物细胞中起着选择性屏障的作用，<ref>{{cite journal | vauthors = Kamiya K, Takeuchi S | title = Giant liposome formation toward the synthesis of well-defined artificial cells | journal = Journal of Materials Chemistry B | volume = 5 | issue = 30 | pages = 5911–5923 | date = August 2017 | pmid = 32264347 | doi = 10.1039/C7TB01322A }}</ref> 因此可以选择磷脂膜作为一个明显的划分界限。科学家通过将生物分子包裹在细胞大小的磷脂小泡中，观察这些分子在生物细胞中的类似作用，从而重建某些细胞功能。<ref>{{cite journal | vauthors = Litschel T, Schwille P | title = Protein Reconstitution Inside Giant Unilamellar Vesicles | journal = Annual Review of Biophysics | volume = 50 | pages = 525–548 | date = May 2021 | pmid = 33667121 | doi = 10.1146/annurev-biophys-100620-114132 }}</ref>类似地，功能性生物构建模块可以被封装在这些脂质隔室中，以实现人工细胞的合成(无论多么初级)。
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人们想到利用合成遗传信息，制备具有DNA自复制能力的磷脂双层囊泡。脂质膜的形成、通过模板过程进行的 DNA 和 RNA 复制、为了在脂膜上进行主动运输的化学能量的收集，是这种人工细胞的三个基本元素。<ref>{{cite journal | vauthors = Szostak JW, Bartel DP, Luisi PL | title = Synthesizing life | journal = Nature | volume = 409 | issue = 6818 | pages = 387–390 | date = January 2001 | pmid = 11201752 | doi = 10.1038/35053176 | s2cid = 4429162 }}</ref><ref>{{cite journal | vauthors = Pohorille A, Deamer D | title = Artificial cells: prospects for biotechnology | journal = Trends in Biotechnology | volume = 20 | issue = 3 | pages = 123–128 | date = March 2002 | pmid = 11841864 | doi = 10.1016/S0167-7799(02)01909-1 | hdl = 2060/20020043286 }}</ref>这个原始细胞将会遇到的主要障碍是创建一个最小的包含所有足够的生命信息的合成DNA，以及细胞发展中不可或缺的非遗传成分的复制，如分子自我组织。<ref>{{cite journal | vauthors = Noireaux V, Maeda YT, Libchaber A | title = Development of an artificial cell, from self-organization to computation and self-reproduction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 9 | pages = 3473–3480 | date = March 2011 | pmid = 21317359 | pmc = 3048108 | doi = 10.1073/pnas.1017075108 | doi-access = free | bibcode = 2011PNAS..108.3473N }}</ref> 不过，人们希望通过这种自下而上的方法，更深入了解关于在细胞层面组织的基本问题和生物生命起源问题。迄今为止，还没有利用生命分子合成出能够自我繁殖的完全人工细胞，尽管目前各种团体正朝着这一目标努力，但它仍然在遥远的未来。<ref>{{cite journal | vauthors = Rasmussen S, Chen L, Nilsson M, Abe S | title = Bridging nonliving and living matter | journal = Artificial Life | volume = 9 | issue = 3 | pages = 269–316 | date = Summer 2003 | pmid = 14556688 | doi = 10.1162/106454603322392479 | s2cid = 6076707 | citeseerx = 10.1.1.101.1606 }}</ref>
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人们想到利用合成遗传信息，制备具有DNA自复制能力的磷脂双层囊泡。脂质膜的形成、通过模板过程进行的 DNA 和 RNA 复制、为了在脂膜上进行主动运输的化学能量的收集，是这种人工细胞的三个基本元素。<ref>{{cite journal | vauthors = Szostak JW, Bartel DP, Luisi PL | title = Synthesizing life | journal = Nature | volume = 409 | issue = 6818 | pages = 387–390 | date = January 2001 | pmid = 11201752 | doi = 10.1038/35053176 }}</ref><ref>{{cite journal | vauthors = Pohorille A, Deamer D | title = Artificial cells: prospects for biotechnology | journal = Trends in Biotechnology | volume = 20 | issue = 3 | pages = 123–128 | date = March 2002 | pmid = 11841864 | doi = 10.1016/S0167-7799(02)01909-1 | hdl = 2060/20020043286 }}</ref>这个原始细胞将会遇到的主要障碍是创建一个最小的包含所有足够的生命信息的合成DNA，以及细胞发展中不可或缺的非遗传成分的复制，如分子自我组织。<ref>{{cite journal | vauthors = Noireaux V, Maeda YT, Libchaber A | title = Development of an artificial cell, from self-organization to computation and self-reproduction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 9 | pages = 3473–3480 | date = March 2011 | pmid = 21317359 | pmc = 3048108 | doi = 10.1073/pnas.1017075108 | doi-access = free | bibcode = 2011PNAS..108.3473N }}</ref> 不过，人们希望通过这种自下而上的方法，更深入了解关于在细胞层面组织的基本问题和生物生命起源问题。迄今为止，还没有利用生命分子合成出能够自我繁殖的完全人工细胞，尽管目前各种团体正朝着这一目标努力，但它仍然在遥远的未来。<ref>{{cite journal | vauthors = Rasmussen S, Chen L, Nilsson M, Abe S | title = Bridging nonliving and living matter | journal = Artificial Life | volume = 9 | issue = 3 | pages = 269–316 | date = Summer 2003 | pmid = 14556688 | doi = 10.1162/106454603322392479| citeseerx = 10.1.1.101.1606 }}</ref>
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另一种方法是，创造一个类似于人们认为在进化过程中存在的，称为原始汤的状态的原始细胞。各种RNA聚合物可以被包封在囊泡中，在如此小的边界条件下，将进行化学反应测试。<ref>{{cite journal| vauthors = Gilbert W |title=Origin of life: The RNA world|journal=Nature|date=20 February 1986 |volume=319 |issue=6055 |pages=618 |doi=10.1038/319618a0 |bibcode=1986Natur.319..618G |s2cid=8026658 }}</ref>
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另一种方法是，创造一个类似于人们认为在进化过程中存在的，称为原始汤的状态的原始细胞。各种RNA聚合物可以被包封在囊泡中，在如此小的边界条件下，将进行化学反应测试。<ref>{{cite journal| vauthors = Gilbert W |title=Origin of life: The RNA world|journal=Nature|date=20 February 1986 |volume=319 |issue=6055 |pages=618 |doi=10.1038/319618a0 |bibcode=1986Natur.319..618G }}</ref>
       
===伦理和争议===
 
===伦理和争议===
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原始细胞的研究引起了争议和反对意见，包括对”人工生命”模糊定义的批评。<ref>{{cite journal | vauthors = Bedau M, Church G, Rasmussen S, Caplan A, Benner S, Fussenegger M, Collins J, Deamer D | display-authors = 6 | title = Life after the synthetic cell | journal = Nature | volume = 465 | issue = 7297 | pages = 422–424 | date = May 2010 | pmid = 20495545 | doi = 10.1038/465422a | s2cid = 27471255 | bibcode = 2010Natur.465..422. }}</ref>尽管对原细胞最普遍的担忧是它们通过不受控制的复制对人类健康和环境的潜在威胁，但创造一个基本的生命单位最紧迫的问题是伦理。<ref name='Beadau'/>
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原始细胞的研究引起了争议和反对意见，包括对”人工生命”模糊定义的批评。<ref>{{cite journal | vauthors = Bedau M, Church G, Rasmussen S, Caplan A, Benner S, Fussenegger M, Collins J, Deamer D | display-authors = 6 | title = Life after the synthetic cell | journal = Nature | volume = 465 | issue = 7297 | pages = 422–424 | date = May 2010 | pmid = 20495545 | doi = 10.1038/465422a | bibcode = 2010Natur.465..422. }}</ref>尽管对原细胞最普遍的担忧是它们通过不受控制的复制对人类健康和环境的潜在威胁，但创造一个基本的生命单位最紧迫的问题是伦理。<ref name='Beadau'/>
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大公司已经在生物领域投入了大量资金，比如与合成基因公司合作的埃克森美孚公司 ExxonMobil、克雷格·文特 Craig Venter的开发藻类燃料的生物合成公司<ref>{{cite journal | vauthors = Sheridan C | title = Big oil bucks for algae | journal = Nature Biotechnology | volume = 27 | issue = 9 | pages = 783 | date = September 2009 | pmid = 19741613 | doi = 10.1038/nbt0909-783 | s2cid = 205270805 }}</ref>
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大公司已经在生物领域投入了大量资金，比如与合成基因公司合作的埃克森美孚公司 ExxonMobil、克雷格·文特 Craig Venter的开发藻类燃料的生物合成公司<ref>{{cite journal | vauthors = Sheridan C | title = Big oil bucks for algae | journal = Nature Biotechnology | volume = 27 | issue = 9 | pages = 783 | date = September 2009 | pmid = 19741613 | doi = 10.1038/nbt0909-783 }}</ref>
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通过将一个完全合成的基因组引入到基因组上空出的宿主细胞中，即创造出了一种人工细胞。<ref name="gibson52">{{cite journal | vauthors = Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, Smith HO, Venter JC | display-authors = 6 | title = Creation of a bacterial cell controlled by a chemically synthesized genome | journal = Science | volume = 329 | issue = 5987 | pages = 52–56 | date = July 2010 | pmid = 20488990 | doi = 10.1126/science.1190719 | s2cid = 7320517 | bibcode = 2010Sci...329...52G }}</ref>尽管由于宿主细胞的细胞质成分和细胞膜被保留下来而不完全是人工合成的，但该工程细胞处于合成基因组的控制之下，能够[[自复制]]。
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通过将一个完全合成的基因组引入到基因组上空出的宿主细胞中，即创造出了一种人工细胞。<ref name="gibson52">{{cite journal | vauthors = Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, Smith HO, Venter JC | display-authors = 6 | title = Creation of a bacterial cell controlled by a chemically synthesized genome | journal = Science | volume = 329 | issue = 5987 | pages = 52–56 | date = July 2010 | pmid = 20488990 | doi = 10.1126/science.1190719| bibcode = 2010Sci...329...52G }}</ref>尽管由于宿主细胞的细胞质成分和细胞膜被保留下来而不完全是人工合成的，但该工程细胞处于合成基因组的控制之下，能够[[自复制]]。
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===历史===
 
===历史===
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20世纪60年代，Thomas Chang研制出了微胶囊，由于它们是由人造材料制成的细胞大小的隔室，后来他称之为“人工细胞”。<ref>{{cite journal | vauthors = Chang TM | title = SEMIPERMEABLE MICROCAPSULES | journal = Science | volume = 146 | issue = 3643 | pages = 524–525 | date = October 1964 | pmid = 14190240 | doi = 10.1126/science.146.3643.524 | s2cid = 40740134 | bibcode = 1964Sci...146..524C }}</ref>这些细胞由尼龙、火棉胶或交联蛋白质的超薄膜组成，其半透性使得小分子可以扩散进出细胞。这些细胞是微米大小，含有细胞，酶，血红蛋白，磁性材料，吸附剂和蛋白质。<ref name="Chang 2007" />
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20世纪60年代，Thomas Chang研制出了微胶囊，由于它们是由人造材料制成的细胞大小的隔室，后来他称之为“人工细胞”。<ref>{{cite journal | vauthors = Chang TM | title = SEMIPERMEABLE MICROCAPSULES | journal = Science | volume = 146 | issue = 3643 | pages = 524–525 | date = October 1964 | pmid = 14190240 | doi = 10.1126/science.146.3643.524| bibcode = 1964Sci...146..524C }}</ref>这些细胞由尼龙、火棉胶或交联蛋白质的超薄膜组成，其半透性使得小分子可以扩散进出细胞。这些细胞是微米大小，含有细胞，酶，血红蛋白，磁性材料，吸附剂和蛋白质。<ref name="Chang 2007" />
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在20世纪70年代，研究人员能够将酶、蛋白质和激素引入到可生物降解的微胶囊中，后来这种微胶囊在诸如莱希－尼亨氏症候群 Lesch–Nyhan syndrome之类的疾病中得到临床应用。<ref>{{cite journal | vauthors = Palmour RM, Goodyer P, Reade T, Chang TM | title = Microencapsulated xanthine oxidase as experimental therapy in Lesch-Nyhan disease | journal = Lancet | volume = 2 | issue = 8664 | pages = 687–688 | date = September 1989 | pmid = 2570944 | doi = 10.1016/s0140-6736(89)90939-2 | s2cid = 39716068 }}</ref>尽管Thomas Chang最初的研究集中在人工红细胞上，但直到20世纪90年代中期，才出现了可生物降解的人工红细胞。<ref>{{cite book | vauthors = Chang TM | title=Blood substitutes | year=1997 | publisher=Karger | location=Basel | isbn=978-3-8055-6584-4 }}</ref>1994年，生物细胞封装的人工细胞首次在临床上用于治疗糖尿病患者，<ref>{{cite journal | vauthors = Soon-Shiong P, Heintz RE, Merideth N, Yao QX, Yao Z, Zheng T, Murphy M, Moloney MK, Schmehl M, Harris M | display-authors = 6 | title = Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation | journal = Lancet | volume = 343 | issue = 8903 | pages = 950–951 | date = April 1994 | pmid = 7909011 | doi = 10.1016/S0140-6736(94)90067-1 | s2cid = 940319 }}</ref>此后，其他类型的细胞，如肝细胞、成体干细胞和基因工程细胞已被封装，并正在研究用于组织再生。<ref>{{cite journal | vauthors = Liu ZC, Chang TM | title = Coencapsulation of hepatocytes and bone marrow stem cells: in vitro conversion of ammonia and in vivo lowering of bilirubin in hyperbilirubemia Gunn rats | journal = The International Journal of Artificial Organs | volume = 26 | issue = 6 | pages = 491–497 | date = June 2003 | pmid = 12894754 | doi = 10.1177/039139880302600607 | s2cid = 12447199 }}</ref><ref>{{cite journal | vauthors = Aebischer P, Schluep M, Déglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE | display-authors = 6 | title = Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients | journal = Nature Medicine | volume = 2 | issue = 6 | pages = 696–699 | date = June 1996 | pmid = 8640564 | doi = 10.1038/nm0696-696 | s2cid = 8049662 }}</ref>
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在20世纪70年代，研究人员能够将酶、蛋白质和激素引入到可生物降解的微胶囊中，后来这种微胶囊在诸如莱希－尼亨氏症候群 Lesch–Nyhan syndrome之类的疾病中得到临床应用。<ref>{{cite journal | vauthors = Palmour RM, Goodyer P, Reade T, Chang TM | title = Microencapsulated xanthine oxidase as experimental therapy in Lesch-Nyhan disease | journal = Lancet | volume = 2 | issue = 8664 | pages = 687–688 | date = September 1989 | pmid = 2570944 | doi = 10.1016/s0140-6736(89)90939-2 }}</ref>尽管Thomas Chang最初的研究集中在人工红细胞上，但直到20世纪90年代中期，才出现了可生物降解的人工红细胞。<ref>{{cite book | vauthors = Chang TM | title=Blood substitutes | year=1997 | publisher=Karger | location=Basel | isbn=978-3-8055-6584-4 }}</ref>1994年，生物细胞封装的人工细胞首次在临床上用于治疗糖尿病患者，<ref>{{cite journal | vauthors = Soon-Shiong P, Heintz RE, Merideth N, Yao QX, Yao Z, Zheng T, Murphy M, Moloney MK, Schmehl M, Harris M | display-authors = 6 | title = Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation | journal = Lancet | volume = 343 | issue = 8903 | pages = 950–951 | date = April 1994 | pmid = 7909011 | doi = 10.1016/S0140-6736(94)90067-1 }}</ref>此后，其他类型的细胞，如肝细胞、成体干细胞和基因工程细胞已被封装，并正在研究用于组织再生。<ref>{{cite journal | vauthors = Liu ZC, Chang TM | title = Coencapsulation of hepatocytes and bone marrow stem cells: in vitro conversion of ammonia and in vivo lowering of bilirubin in hyperbilirubemia Gunn rats | journal = The International Journal of Artificial Organs | volume = 26 | issue = 6 | pages = 491–497 | date = June 2003 | pmid = 12894754 | doi = 10.1177/039139880302600607 }}</ref><ref>{{cite journal | vauthors = Aebischer P, Schluep M, Déglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE | display-authors = 6 | title = Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients | journal = Nature Medicine | volume = 2 | issue = 6 | pages = 696–699 | date = June 1996 | pmid = 8640564 | doi = 10.1038/nm0696-696}}</ref>
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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。<ref>{{cite journal | vauthors = Chang TM | title = The in vivo effects of semipermeable microcapsules containing L-asparaginase on 6C3HED lymphosarcoma | journal = Nature | volume = 229 | issue = 5280 | pages = 117–118 | date = January 1971 | pmid = 4923094 | doi = 10.1038/229117a0 | s2cid = 4261902 | bibcode = 1971Natur.229..117C }}</ref>这种治疗延缓了肿瘤的发生和生长。<ref>{{cite journal | vauthors = Yu B, Chang TM | title = Effects of long-term oral administration of polymeric microcapsules containing tyrosinase on maintaining decreased systemic tyrosine levels in rats | journal = Journal of Pharmaceutical Sciences | volume = 93 | issue = 4 | pages = 831–837 | date = April 2004 | pmid = 14999721 | doi = 10.1002/jps.10593 }}</ref>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。<ref>{{cite journal | vauthors = Meadows GG, Pierson HF, Abdallah RM, Desai PR | title = Dietary influence of tyrosine and phenylalanine on the response of B16 melanoma to carbidopa-levodopa methyl ester chemotherapy | journal = Cancer Research | volume = 42 | issue = 8 | pages = 3056–3063 | date = August 1982 | pmid = 7093952 }}</ref>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。<ref>{{cite journal | vauthors = Chang TM | title = Artificial cell bioencapsulation in macro, micro, nano, and molecular dimensions: keynote lecture | journal = Artificial Cells, Blood Substitutes, and Immobilization Biotechnology | volume = 32 | issue = 1 | pages = 1–23 | date = February 2004 | pmid = 15027798 | doi = 10.1081/bio-120028665 | s2cid = 37799530 }}</ref>
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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。<ref>{{cite journal | vauthors = Chang TM | title = The in vivo effects of semipermeable microcapsules containing L-asparaginase on 6C3HED lymphosarcoma | journal = Nature | volume = 229 | issue = 5280 | pages = 117–118 | date = January 1971 | pmid = 4923094 | doi = 10.1038/229117a0| bibcode = 1971Natur.229..117C }}</ref>这种治疗延缓了肿瘤的发生和生长。<ref>{{cite journal | vauthors = Yu B, Chang TM | title = Effects of long-term oral administration of polymeric microcapsules containing tyrosinase on maintaining decreased systemic tyrosine levels in rats | journal = Journal of Pharmaceutical Sciences | volume = 93 | issue = 4 | pages = 831–837 | date = April 2004 | pmid = 14999721 | doi = 10.1002/jps.10593 }}</ref>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。<ref>{{cite journal | vauthors = Meadows GG, Pierson HF, Abdallah RM, Desai PR | title = Dietary influence of tyrosine and phenylalanine on the response of B16 melanoma to carbidopa-levodopa methyl ester chemotherapy | journal = Cancer Research | volume = 42 | issue = 8 | pages = 3056–3063 | date = August 1982 | pmid = 7093952 }}</ref>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。<ref>{{cite journal | vauthors = Chang TM | title = Artificial cell bioencapsulation in macro, micro, nano, and molecular dimensions: keynote lecture | journal = Artificial Cells, Blood Substitutes, and Immobilization Biotechnology | volume = 32 | issue = 1 | pages = 1–23 | date = February 2004 | pmid = 15027798 | doi = 10.1081/bio-120028665}}</ref>
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在某些癌症中，人工细胞酶疗法对于激活诸如异环磷酰胺之类的前药也很有意义。将细胞色素 p450酶包裹在人工细胞中，将其转化为活性药物，可以特制地在胰腺癌中积累，或将人工细胞移植到肿瘤部位附近。在这里，被激活的异环磷酰胺的局部浓度将远远高于身体其他部位，从而防止全身中毒。<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>这种治疗在动物身上取得了成功，<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>在 I/II 期临床试验中，晚期胰腺癌患者的生存率中位数增加了一倍，一年生存率增加了两倍。<ref name=Lohr/>
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在某些癌症中，人工细胞酶疗法对于激活诸如异环磷酰胺之类的前药也很有意义。将细胞色素 p450酶包裹在人工细胞中，将其转化为活性药物，可以特制地在胰腺癌中积累，或将人工细胞移植到肿瘤部位附近。在这里，被激活的异环磷酰胺的局部浓度将远远高于身体其他部位，从而防止全身中毒。<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}}</ref>这种治疗在动物身上取得了成功，<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 }}</ref>在 I/II 期临床试验中，晚期胰腺癌患者的生存率中位数增加了一倍，一年生存率增加了两倍。<ref name=Lohr/>
       
====基因疗法 Gene therapy====
 
====基因疗法 Gene therapy====
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在基因疾病的治疗中，基因疗法旨在插入、改变或移除受影响个体细胞内的基因。该技术严重依赖于病毒载体，这引起了对插入突变和系统免疫反应的关注，它们在临床试验中导致了人类死亡<ref>{{cite journal | vauthors = Carmen IH | title = A death in the laboratory: the politics of the Gelsinger aftermath | journal = Molecular Therapy | volume = 3 | issue = 4 | pages = 425–428 | date = April 2001 | pmid = 11319902 | doi = 10.1006/mthe.2001.0305 }}</ref><ref>{{cite journal | vauthors = Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML | display-authors = 6 | title = Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer | journal = Molecular Genetics and Metabolism | volume = 80 | issue = 1-2 | pages = 148–158 | date = 1 September 2003 | pmid = 14567964 | doi = 10.1016/j.ymgme.2003.08.016 }}</ref>和白血病的发展<ref>{{cite journal | vauthors = Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL, Fischer A | display-authors = 6 | title = Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease | journal = Science | volume = 288 | issue = 5466 | pages = 669–672 | date = April 2000 | pmid = 10784449 | doi = 10.1126/science.288.5466.669 | bibcode = 2000Sci...288..669C }}</ref><ref>{{cite journal | vauthors = Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R, Forster A, Fraser P, Cohen JI, de Saint Basile G, Alexander I, Wintergerst U, Frebourg T, Aurias A, Stoppa-Lyonnet D, Romana S, Radford-Weiss I, Gross F, Valensi F, Delabesse E, Macintyre E, Sigaux F, Soulier J, Leiva LE, Wissler M, Prinz C, Rabbitts TH, Le Deist F, Fischer A, Cavazzana-Calvo M | display-authors = 6 | title = LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1 | journal = Science | volume = 302 | issue = 5644 | pages = 415–419 | date = October 2003 | pmid = 14564000 | doi = 10.1126/science.1088547 | s2cid = 9100335 | bibcode = 2003Sci...302..415H }}</ref>。利用裸DNA或质粒DNA作为载体载体本身的传递系统，避免了载体的需要，同时也遇到了系统传递效率低、组织靶向性差等问题。<ref name=Prakash/>
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在基因疾病的治疗中，基因疗法旨在插入、改变或移除受影响个体细胞内的基因。该技术严重依赖于病毒载体，这引起了对插入突变和系统免疫反应的关注，它们在临床试验中导致了人类死亡<ref>{{cite journal | vauthors = Carmen IH | title = A death in the laboratory: the politics of the Gelsinger aftermath | journal = Molecular Therapy | volume = 3 | issue = 4 | pages = 425–428 | date = April 2001 | pmid = 11319902 | doi = 10.1006/mthe.2001.0305 }}</ref><ref>{{cite journal | vauthors = Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML | display-authors = 6 | title = Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer | journal = Molecular Genetics and Metabolism | volume = 80 | issue = 1-2 | pages = 148–158 | date = 1 September 2003 | pmid = 14567964 | doi = 10.1016/j.ymgme.2003.08.016 }}</ref>和白血病的发展<ref>{{cite journal | vauthors = Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL, Fischer A | display-authors = 6 | title = Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease | journal = Science | volume = 288 | issue = 5466 | pages = 669–672 | date = April 2000 | pmid = 10784449 | doi = 10.1126/science.288.5466.669 | bibcode = 2000Sci...288..669C }}</ref><ref>{{cite journal | vauthors = Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R, Forster A, Fraser P, Cohen JI, de Saint Basile G, Alexander I, Wintergerst U, Frebourg T, Aurias A, Stoppa-Lyonnet D, Romana S, Radford-Weiss I, Gross F, Valensi F, Delabesse E, Macintyre E, Sigaux F, Soulier J, Leiva LE, Wissler M, Prinz C, Rabbitts TH, Le Deist F, Fischer A, Cavazzana-Calvo M | display-authors = 6 | title = LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1 | journal = Science | volume = 302 | issue = 5644 | pages = 415–419 | date = October 2003 | pmid = 14564000 | doi = 10.1126/science.1088547| bibcode = 2003Sci...302..415H }}</ref>。利用裸DNA或质粒DNA作为载体载体本身的传递系统，避免了载体的需要，同时也遇到了系统传递效率低、组织靶向性差等问题。<ref name=Prakash/>
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与血液透析相比，人工细胞血液灌流被认为是一种成本更低、效率更高的解毒方法。<ref name="Chang 2007"/>在血液灌流中，成千上万的吸附性人工细胞通过在病人血液灌流的两端使用两个筛子被保存在一个小容器内。随着血液循环，毒素或药物扩散进入细胞，并被吸收材料所保留。人工细胞的细胞膜比透析用细胞的细胞膜要薄得多，细胞膜的小体积意味着细胞膜的表面积很大。这意味着一部分细胞理论上的质量传递比整个人工肾脏机器的质量传递高百倍。<ref name='Chang 2007' />该装置已被确立为治疗意外或自杀性中毒患者的常规临床方法，但也被引入治疗肝功能衰竭和肾功能衰竭，以实现这些器官的部分功能。<ref name= 'Chang 2007' />人工细胞血液灌流也被提议用于免疫吸附，通过在人工细胞表面粘附免疫吸附材料，如白蛋白，可将抗体从体内除去。这一原理已被应用于从骨髓移植患者血浆中去除血型抗体，<ref>{{cite journal | vauthors = Bensinger WI, Buckner CD, Clift RA | title = Whole blood immunoadsorption of anti-A or anti-B antibodies | journal = Vox Sanguinis | volume = 48 | issue = 6 | pages = 357–361 | year = 1985 | pmid = 3892895 | doi = 10.1111/j.1423-0410.1985.tb00196.x | s2cid = 12777645 }}</ref>以及通过单克隆抗体去除低密度脂蛋白治疗高胆固醇血症。<ref>{{cite journal | vauthors = Yang L, Cheng Y, Yan WR, Yu YT | title = Extracorporeal whole blood immunoadsorption of autoimmune myasthenia gravis by cellulose tryptophan adsorbent | journal = Artificial Cells, Blood Substitutes, and Immobilization Biotechnology | volume = 32 | issue = 4 | pages = 519–528 | year = 2004 | pmid = 15974179 | doi = 10.1081/bio-200039610 | s2cid = 7269229 }}</ref>血液灌流在血液透析制造业薄弱的国家尤其有用，因为那里的血液透析设备往往更便宜，而且用于肾衰竭患者。
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与血液透析相比，人工细胞血液灌流被认为是一种成本更低、效率更高的解毒方法。<ref name="Chang 2007"/>在血液灌流中，成千上万的吸附性人工细胞通过在病人血液灌流的两端使用两个筛子被保存在一个小容器内。随着血液循环，毒素或药物扩散进入细胞，并被吸收材料所保留。人工细胞的细胞膜比透析用细胞的细胞膜要薄得多，细胞膜的小体积意味着细胞膜的表面积很大。这意味着一部分细胞理论上的质量传递比整个人工肾脏机器的质量传递高百倍。<ref name='Chang 2007' />该装置已被确立为治疗意外或自杀性中毒患者的常规临床方法，但也被引入治疗肝功能衰竭和肾功能衰竭，以实现这些器官的部分功能。<ref name= 'Chang 2007' />人工细胞血液灌流也被提议用于免疫吸附，通过在人工细胞表面粘附免疫吸附材料，如白蛋白，可将抗体从体内除去。这一原理已被应用于从骨髓移植患者血浆中去除血型抗体，<ref>{{cite journal | vauthors = Bensinger WI, Buckner CD, Clift RA | title = Whole blood immunoadsorption of anti-A or anti-B antibodies | journal = Vox Sanguinis | volume = 48 | issue = 6 | pages = 357–361 | year = 1985 | pmid = 3892895 | doi = 10.1111/j.1423-0410.1985.tb00196.x }}</ref>以及通过单克隆抗体去除低密度脂蛋白治疗高胆固醇血症。<ref>{{cite journal | vauthors = Yang L, Cheng Y, Yan WR, Yu YT | title = Extracorporeal whole blood immunoadsorption of autoimmune myasthenia gravis by cellulose tryptophan adsorbent | journal = Artificial Cells, Blood Substitutes, and Immobilization Biotechnology | volume = 32 | issue = 4 | pages = 519–528 | year = 2004 | pmid = 15974179 | doi = 10.1081/bio-200039610}}</ref>血液灌流在血液透析制造业薄弱的国家尤其有用，因为那里的血液透析设备往往更便宜，而且用于肾衰竭患者。
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====微囊肝细胞 Encapsulated hepatocytes====
 
====微囊肝细胞 Encapsulated hepatocytes====
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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。<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>实验中，肝细胞附着在微载体表面，<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>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。<ref name="Dixit" />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。<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>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。<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>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。<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>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。
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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。<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>实验中，肝细胞附着在微载体表面，<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>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。<ref name="Dixit" />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。<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>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。<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}}</ref>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。<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>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。
       
====微囊细菌细胞 Encapsulated bacterial cells====
 
====微囊细菌细胞 Encapsulated bacterial cells====
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口服活菌群，目前正用于治疗调节肠道菌群，<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>预防腹泻疾病，<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>治疗幽门螺杆菌感染，特应性炎症，<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>乳糖不耐受<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>和免疫调节<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>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。<ref name="Prakash" />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。<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>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。<ref name="Prakash" />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。<ref name="Prakash" />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，<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>以及促进免疫系统产生Ig分泌细胞。<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>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。<ref name="Prakash" />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。<ref name="Prakash" />
+
口服活菌群，目前正用于治疗调节肠道菌群，<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>预防腹泻疾病，<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 }}</ref>治疗幽门螺杆菌感染，特应性炎症，<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}}</ref>乳糖不耐受<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 }}</ref>和免疫调节<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>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。<ref name="Prakash" />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。<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>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。<ref name="Prakash" />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。<ref name="Prakash" />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，<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>以及促进免疫系统产生Ig分泌细胞。<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>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。<ref name="Prakash" />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。<ref name="Prakash" />
    
====人工血细胞作为氧载体 Artificial blood cells as oxygen carriers====
 
====人工血细胞作为氧载体 Artificial blood cells as oxygen carriers====
第164行： 第164行：     
===杰瓦努 Jeewanu===
 
===杰瓦努 Jeewanu===
−
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。<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>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。<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>
+
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。<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| archive-url = https://web.archive.org/web/20140323225723/http://www.ias.ac.in/jbiosci/grote_3677.pdf | archive-date = 2014-03-23 }}</ref>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。<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>
      −
== See also ==
+
== 参见 ==
 
* [[原始细胞]]  
 
* [[原始细胞]]  
 
* [[合成生物学]]  
 
* [[合成生物学]]  
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