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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.

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.

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.

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.

====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.

 

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.

====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/>

 

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.

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。

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.

====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.

====Artificial leuko-polymersomes ====

====Artificial leuko-polymersomes ====

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.

==Unconventional types of artificial cells==

==Unconventional types of artificial cells==

===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.

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。

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。

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。

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.

== 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]]  

 

== References ==

== References ==