Table 2.
Artificial Cells (AC): Timeline of ideas first reported (references available from [5])
| 1957 Chang | First artificial cells prepared with a synthetic membrane to replace RBC membrane and containing hemoglobin and red blood cell enzymes (emulsion phase separation, extrusion method or spray coating) |
| 1964 Chang (Science) | Artificial cells (AC) containing enzymes, hemoglobin and cells formed by interfacial coacervation or interfacial polymerization to form membranes of polymer, crosslinked protein, polymer conjugated with protein, also crosslinked protein microspheres |
| 1964, 1965 Chang | Nanobiotechnology: crosslinked protein (polyHb) & conjugated Hb |
| 1964, 1965 Chang 1966 Chang et al. | Extrusion drop method for AC to encapsulate intact cells for immunoisolation in cell therapy. |
| 1965 Bangham et al. | Liquid crystal microspheres of multi-lamellar lipid (liposomes) as membrane model for basic research |
| 1965, 1972a, 1973b Chang | AC for molecular sieve chromatography and separation |
| 1965 Chang 1966 Chang et al. | AC with intracellular multi-compartments |
| 1966 Chang | Silastic AC and microspheres containing protein. |
| 1966 Chang | AC containing magnetic materials and biological materials. |
| 1966, 1969a Chang | Ultrathin membrane AC containing adsorbents for hemoperfusion |
| 1966 Clark & Gollan | Fluorocarbon as oxygen carrier |
| 1967 Chang et al. | AC with polysaccharide complexed membrane for biocompatibility |
| 1968 Chang & Poznansky (Nature) | Implanted enzyme AC for enzyme therapy in inborn error of metabolism (shown in congenital catalase-deficient acatalesemic mice) |
| 1968 Bunn & Jandl | Intramolecularly crosslinked single Hb molecule |
| 1968 Geyer et al. | Fluorocarbon effective in exchange transfusion in animal studies |
| 1969d Chang 1972a Chang | AC with lipid-polymeric membrane or lipid-crosslinked protein membrane containing cyclic transport carrier. (AC contains proteins) |
| 1970–1975 Chang et al. | First clinical use of artificial cells in patients (in hemoperfusion) |
| 1971a Chang (Nature) | Implanted enzyme AC for lymphosarcoma suppression in mice |
| 1971b Chang | Nanobiotechnology: glutaraldehyde crosslinked Hb into polyHb. Later, others used this method for blood substitutes in patients. |
| 1972a Chang | First monograph on Artificial Cells |
| 1972b Chang (Lancet) | AC hemoperfusion resulted in Grade IV hepatic coma patient recovering consciousness. |
| 1973 Gregoriadis | First use of liposomes to entrap enzymes & drugs. Led to extensive development of liposomes as delivery systems |
| 1975h Chang | Paper discussing one shot vaccine using AC |
| 1976a Chang | Biodegradable polylactide microcapsules and microparticles containing proteins & hormones |
| 1976 Tam, Blumenstein & Wong | Soluble dextran conjugated hemoglobin |
| 1976 Bonhard et al. | Develop glutaraldehyde crosslinked polyHb as blood substitute |
| 1977–1985 Chang with Campbell, Cousineau, Ilan, Grunwald, Wahl, Yu, etc. | Artificial cells containing multienzyme systems with cofactor recyclying for multistep enzyme reactions. |
| 1978 Naito & Yokoyama | Developed perfluorodecalin as blood substitute towards clinical trials |
| 1980 Lim & Sun (Science) | Alginate-polylysine-alginate AC encapsulated cells |
| 1980 Rosenthal & Chang | AC membrane of lipid-protein-polymer containing Na+K+-ATPase |
| 1980 Djordjevich & Miller | Lipid membrane AC encapsulated hemoglobin |
| 1985 Mitsuno & Ohyanagi | Clinical trials of perfluorodecalin as red blood cell substitute |
| 1986 Yuan & Chang | AC containing microsomes & cytosol |
| 1986 Bourget & Chang | Oral enzyme AC for inborn error of metabolism (Phenyketonuria rat) |
| 1986 Sipehia, Bannard & Chang | AC membrane that exclude small hydrophilic molecules but permeable to large lipophilic molecules |
| 1986 Chang, Bourget & Lister | Novel finding of extensive enterorecirculation of amino acids leading to the use of oral enzyme AC therapy to selectively remove specific unwanted systemic amino acid. |
| 1988 Tsuchida’s group 2002 Tsuchida et al. | Development and in-vivo testing of synthetic heme complex either to liposome or to recombinant albumin as blood substitute. |
| 1989a Chang, 1989 Palmour et al., Chang | Clinical use of oral enzyme artificial cells in a patient (patient with an inborn error of metabolism: Lesch-Nyhan disease) |
| 1989 Moss et al. | Clinical trials with glutaraldehyde crosslinked PolyHb |
| 1990 Hoffmann et al. | Recombinant human hemoglobin |
| 1994 Yu & Chang | Biodegradable polymeric membrane nano-artificial red blood cells |
| 1994 Soon-Shiong et al. | AC encapsulated islet transplantation in a type 1 diabetic patient. Insulin independence reported. |
| 1996 Prakash & Chang (Nature Medicine) | Oral artificial cells containing genetically engineered cells lowers systemic urea in an uremic rats model |
| 1996 Aebischer, Lysagth et al. (Nature Medicine) | Polymeric fiber encapsulation of genetically modified xenogeneic cells for intrathecal delivery of CNTF in amyotrophic lateral sclerosis patients |
| 1998 D’Agnillo & Chang (Nature Biotechnology) | Nanobiotechnology of crosslinking of Hb, catalase and superoxide dismutase to form soluble nanodimension PolyHb-CAT-SOD |
| 1998 Tsuchida | Lipid AC vesicle Hb: Develop and test in animal towards clinical use |
| 1999 Philips et al. | PEG-lipid membrane AC containing Hb increases circulation time |
| 2000 Liu & Chang | AC coencapsulating hepatocytes and adult stem cells |
| 2001 Lörh et al. (Lancet) | Clinical trial of AC microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma in patients |
| 2002 Gould et al. | The life-sustaining capacity of human polyhemoglobin in trauma surgery clinical trials |
| 2002 Sprung et al. | The use of bovine polyhemoglobin in surgical patients: results of a multicenter, randomized, single-blinded trial |
| 2003 Chang, Powanda, Yu | PEG-PLA membrane AC containing Hb & rbc enzymes |
| 2004 Bloch et al., Aebischer | Phase I clinical study for Huntington’s Disease, using encapsulated cells engineered to secrete Human Ciliary Neurotrophic Factor |
| 2004 Yu & Chang (Melanoma Res J) | Nanobiotechnological approach of PolyHb-tyrosinase: delays the growth of melanoma in a rat model |
| 2006 Liu & Chang (J Liver Transplantation) | AC encapsulated bone marrow stem cells regenerate liver resulting in recovery and survival of rats with 90% of liver surgically removed |