Abstract
Over a thousand combinations of polyanions and polycations were tested to search for new polymer candidates that would be suitable for encapsulation of living cells. The combination of sodium alginate, cellulose sulfate, poly (methylene-co-guanidine) hydrochloride, calcium chloride, and sodium chloride was most promising. In parallel, a novel multiloop chamber reactor was developed to control the time of complex formation and to negate gravitational effects such as pancreatic islet sedimentation and droplet deformation during the encapsulation process. Encapsulated rat islets demonstrated glucose-stimulated insulin secretion in vitro, and reversed diabetes in mice. This new capsule formulation and encapsulation system allows independent adjustments of capsule size, wall thickness, mechanical strength, and permeability, which may offer distinct advantages for immunoisolating cells.
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References
Colton, C.K. and Avgoustiniatos, E.S. 1991. Bioengineering in development of the hybrid artificial pancreas. J. Biomechanical Engineering 113: 152–170.
Lanza, R.P., Sullivan, S.J., and Chick, W.L. 1992. Islet transplantation with immunoisolation. Diabetes 41: 1503–1510.
Chang, T.M. 1992. Hybrid artificial cells: microencapsulation of living cells. ASAIO Journal 38: 128–130.
Maki, T., Mullon, C.J., Solomon, B.A., and Monaco, A.P. 1995. Novel delivery of pancreatic islet cells to treat insulin-dependent diabetes mellitus. Clin. Pharmacokinetics 28: 471–482.
Reach, G. 1994. Bioartificlal pancreas. Transplantation Proceedings 26: 397–398.
Lacy, R.E. 1995. Treating diabetes with transplanted cells. Scientific American 273: 50–58.
Ricordi, C. 1992. Pancreatic islet cell transplantation. R.G. Landes Company, Austin, TX.
Lanza, R.R., Kuehtreiber, W.M., Ecker, D., Staruk, J.E., and Chick, W.L. 1995. Xenotransplantation of porcine and bovine islets without immunosuppression using uncoated alginate microspheres. Transplantation 59: 1377–1384.
Lanza, R.P., Beyer, A.M., and Chick, W.L. 1994. Xenogenic humoral responses to islets transplanted In biohybrid diffusion chambers. Transplantation 57: 1371–1375.
O'Shea, G.M., and Sun, A.M. 1986. Encapsulation of rat islets of Langerhans prolongs xenograft survival in diabetic mice. Diabetes 35: 943–946.
Lanza, R.P., Butler, D.H., Borland, K.M., Staruk, J.E., Faustman, D.L., Solomon, B.A. et al. 1991. Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression. Proc. Nat. Acad. Sci. USA 88: 11100–11104.
Lum, Z.P., Tai, I.T., Krestow, M., Norton, J., Vacek, I., and Sun, A.M. 1991. Prolonged reversal of diabetic state in NOD mice by xenografts of microencap-sulated rat islets. Diabetes 40: 1511–1516.
Soon-Shiong, P., Feldman, E., Nelson, R., Heintz, R., Yao, Q., Yao, Z. et al. 1993. Long-term reversal of diabetes by the injection of immunoprotected islets. Proc. Nat. Acad. Sci. USA 90: 5843–5847.
Soon-Shiong, P., Heintz, R.E., Merideth, N., Yao, Q.X., Yao, Z., Zheng, T. et al. 1994. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 343: 950–951.
Scharp, D.W., Swanson, C.J., Olack, B.J., Latta, P.P., Hegre, O.D., Doherty, E.J. et al. 1994. Protection of encapsulated human islets implanted without immunosuppression in patients with type I or type II diabetes and in nondiabetic control subjects. Diabetes 43: 1167–1170.
Weber, C., Krekun, S., Koschitzky, T., Zabinski, S., D'Agati, V., Hardy, M. et al. 1991. Prolonged functional survival of rat-to-NOD mouse Islet xenografts by ultraviolet-B (UV-B) irradiation plus microencapsulation of donor islets. Transplantation Proceedings 23: 764–766.
Calafiore, R., Basta, G., Osticioli, L., Luca, G., Tortoioli, C., and Brunetti, P. 1996. Coherent microcapsules for pancreatic islet transplantation: a new approach for bioartificial pancreas. Transplantation Proceedings 28: 812–813.
Lim, F., and Sun, A.M. 1980. Microencapsulated islets as bioartificial endocrine pancreas. Science 210: 908–910.
Goosen, M.F.A. 1994. pp. 21–44 in Immunoisolation of pancreatic islets. Lanza, R.R and Chick, W.L. (eds). R.G. Landes Company, Austin, TX.
De Vos, P., Wolters, G.H.J., Fritschy, W.M., and van Schilfgaarde, R. 1993. Obstacles in the application of microencapsulation in islet transplantation. Int. J. Artifical Organs 16: 205–212.
Goosen, M.F.A., O'Shea, G., Gharapetian, H.M., Chou, S., and Sun, A.M. 1985. Optimization of microencapsulation parameters: semipermeable microcapsules as a bioartificial pancreas. Biotechnol. Bioeng. 27: 146–150.
Crooks, C.A., Douglas, J.A., Broughton, R.L., and Sefton, M.V. 1990. Microencapsulation of mammalian cells in a HEMA-MMA copolymer: effects on capsule morphology and permeability. J. Biomed. Mat. Res. 24: 1241–1262.
Kendall, J.M., Lee, M.C., and Wang, T.G. 1982. Fluid and chemical dynamics relating to encapsulation technology. J. Vacuum Sci. Tech. 20: 1091.
Kendall, J.M. 1986. Experiments on annular liquid jet instability and on the formation of liquid shells. Physical Fluids 29: 2086–2094.
Lee, C.P., and Wang, T.G. 1988. The centering dynamics of a thin liquid shell in capillary oscillations. J. Fluid Mech. 188: 411–435.
Lin, K.C. and Wang, T.G. 1992. A novel method for producing microspheres with semipermeabile polymer membranes. AIAA 92-0118.
Kendall, J.M., Chang, M., and Wang, T.G. 1988. Fluid and chemical dynamics relating to encapsulation technology. Am. Inst. Physics Proc. 197: 487–495.
Lardner, T. and Pujara, P. 1980. Compression of spherical cells. Mechanics Today 5: 161–176.
Brissová, M., Lacík, I., Powers, A.C., and Wang, T.G. 1996. Evaluation of microcapsule permeability via insverse size exclusion chromatography. Analytical Biochemistry 242: 104–111.
Nave, R., Weber, K., and Potschka, M. 1993. Universal calibration of size-exclusion chromatography for proteins in guanidinium hydrochoride including the high-molecular-mass proteins titin and nebulin. J. Chromatography A654: 229–246.
Sun, Y.L., Ma, X., Zhou, D., Vacek, I., and Sun, A.M. 1993. Porcine pancreatic islets: isolation, microencapsulation, and Xenotransplantation. Artificial Organs 17: 727–733.
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Wang, T., Lacík, I., Brissová, M. et al. An encapsulation system for the immunoisolation of pancreatic islets. Nat Biotechnol 15, 358–362 (1997). https://doi.org/10.1038/nbt0497-358
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DOI: https://doi.org/10.1038/nbt0497-358
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