Abstract
It is estimated that approximately 1.4 million people in the United States suffer from insulin dependent diabetes mellitus (IDDM). Daily insulin therapy and whole organ pancreas transplantation are the only treatments currently available. Results of the diabetes complications and control trial have indicated that while tight control of circulating glucose levels significantly reduced the complications associated with IDDM, it does not prevent them. Insulin replacement therapy is not sufficient to prevent the macrovascular and microvascular complications that make IDDM the third leading cause of death. Pancreas transplant suffers from a shortage of donor organs and requires that the recipient be placed on lifelong immunosuppressive therapy. Adult islet transplantation has met with little success and also suffers from a shortage of donor organs and the need for potent immunosuppression. In contrast, human fetal pancreas (HFP) is readily available, has the potential for further growth and differentiation following transplantation and can be cultured in vitro. This gives HFP the potential for immunologic manipulation such that immunosuppressive therapy may be significantly reduced or eliminated. The growth and differentiation of HFP may be accelerated with short-term culture in growth factors.
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References
Hullett, D. A., Falany, J.L., Love, R.B., Burlingham, W.J., Pan, M., and Sollinger, H.W. Human fetal pancreas -a potential source for transplantation. Transplantation 1987;43:18.
Tuch, B.E., and Simpson, A.M. Experimental fetal islet transplantation. In: Pancreatic Islet Cell Transplantation Ricordi, C. ed. R.C. Landers, Co., Austin, TX. 1992. p294.
Bethke, K.P., Hullett, D.A., Falany, J.L., Love, R.B., and Sollinger, H.W. Cultured human fetal pancreatic tissue reverses experimentally induced diabetes in nude mice. Curr. Surg. 1988;45(2): 123.
Hullett, D.A., Landry, A.S., Leonard, D.K., and Sollinger, H.W. Improved human fetal pancreatic tissue survival following hyperbaric oxygen culture. Transplan. Proc. 1989;21(1):2659.
Hullett, D.A., Bethke, K.P., Landry, A.S., Leonard, D.K., and Sollinger, H.W. Successful long-term cryopreservation and transplantation of human fetal pancreas. Diabetes 1989;38(4):448.
Eckhoff, D.E., Sollinger, H.W., and Hullett, D.A. Selective enhancement of B cell activity by preparation of fetal pancreatic proislets and culture with insulin growth factor 1 (IGF-1). Transplantation 1991;51(6):1161.
Lafferty, K.J., and Hao, L. Fetal pancreas transplantation for treatment of IDDM patients. Diabets Care 1993;16:383.
Mandel, T.E., and Koulmanda, M. Effect of culture conditions on fetal mouse pancreas in vitro and after transplantation in syngeneic and allogeneic recipients. Diabetes 1985;34:1082.
Simeonovic, C.J., Hodden, M.J., and Hume, D.A. Role of la-positive leukocytes and F4/80 positive macrophages in the immunogeneity of fetal mouse proislets and fetal pancreas. Transplant. Proc. 1988;20:68.
Simeonovic, C.J., and Lafferty, K.J. Immunogeniety of isolated fetal mouse pancreas. Aust. J. Exp. Biol. Med. Sci. 1982;60:391.
Hullett, D.A., Landry, A.S., Leonard, D.K., and Sollinger, H.W. Enhancement of thryoid allograft survival following organ culture: alteration of tissue immunogenicity. Transplantation 1989;47(1):24.
LaRosa, F.B., and Talmage, D.W. The failure of major histocompatibility antigen to stimulate a thyroid allograft reaction after culture in oxygen. J. Exp. Med. 1983; 157:898.
Talmage, D.W., and Dart, G.A. Effect of oxygen pressure during culture on survival of mouse thyroid allografts. Science 1978;200:1066.
Lafferty, K.J., Bootes, A., Kilby, A. A., and Barch, W. Mechanism of thyroid allograft rejection. Aust. J. Exp. Biol. Sci. 1976;54:573.
Hardy, M.A. Reemtsma, K. Lau, H.T. Induction of indefinite rat islet allograft survival with direct ultraviolet irradiation and peri-transplant cyclosporine. Transplant. Proc. 1985; 17:423.
Markmann, J.F., Tomaszewski, J., Posselt, A.N., Levy, A.R., Woehrle, M., Barker, C.F., and Naji, A. The effect of islet cell culture in vitro at 24°C on graft survival and MHC antigen expression. Transplantation 1990;49:272.
LaRosa, F.G., Smilek, D., Talmage, D.W., Lafferty, K.J., Bauling, P., and Ammons, T.J. Evidence that tolerance to cultured thyroid allografts is an active immunological process. Protection of third party grafts bearing new antigens when associated with tolerogenic antigens.Transplantation 1992;53:903.
Simon, J.C., Tigelaar, R.E., Bergstresser, P.R., Edelbaum, D., Cruz, P.D.Jr., Ultaviolet B radiation converts langerhans cells from immunogenic to tolerogenic antigen-presenting cells. J. Immunol. 1991;145(2):485.
Everlith, K.M., Landry, A.S., Sollinger, H.W., and Hullett, D.A. Induction of recipient tolerance by hyperbaric oxygen culture may be mediated by anergic CD8+ T cells. Transplant. Sci. 1993;3:20.
Rosenberg, L., Vinik, A.I., and Duguid, W.P. Islet neogenesis. In: Pancreatic Islet Cell Transplantation. Ricordi, C., ed. R.C. Landers, Co. Austin, TX, 1992; p.58.
Smith, F.E., Rosen, K.M., Villa-Komaroff, L. Wier, G.C., and Bonner-Wier, S. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas. Proc. Nat’l. Acad. Sci. USA 1991 ;88:6152.
Korsgren, O., Andersson, A., and Sandler, S. Pretreatment of fetal porcine pancreas in culture with nicotinamide accelerates reversal of diabetes after transplantation to nude mice. Surgery 1993; 113:205.
Gu, D., and Sarvetnick, N. Epithelial cell proliferation and islet neogenesis in IFN-γ transgenic mice. Development 1993;118:33
Welsh, N., Svensson, C., and Welsh, M. Content of adenine nucleotide translocator mRNA in insulin-producing cells of different functional states. Diabetes 1989;38:1377.
Beattie, G.M., Levine, F., Mally, M.I., Otonkoski, T., O’Brien, J.S., Salomon, D.R., and Hayek, A. Acid β-galactosidase: a developmentally regulated marker of endocrine cell precursors in the human fetal pancreas. J. Clin. Endocrinol, and Metab. 1994;78:1232.
Watanabe, T., Yonemura, Y., Yonekura, H., Suzuki, Y, Miyashita, H., Sugiyama, K., Moriizumi, S., Unno, M., Tanaka, O., Kondo, H., Bone, A.J., Takasawa, S., and Okamoto, H. Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein. Proc. Nat’l. Acad. Sci. USA 1994;91:3589.
Otonkoski, T., Mally, M.I., and Hayek, A. Opposite effects of β-cell differentiation and growth on reg expression in human fetal pancreatic cells. Diabetes 1994;43:1164.
Sjoholm, A., and Hellerstrom, C. TGF-β stimulates insulin secretion and blocks mitogenic response of pancreatic β-cells to glucose. Am. J. Physiol. 1991;363:C1046.
Wang, T.C., Bonner-Wier, S., Oates, P.S., Chulak, M. Simon, B., Merlino, G.T., Schmidt, E.V., and Brand, S.J. Pancreatic gastrin stimulates islet differentiation of transforming growth factor α-induced ductular presursor cells. J. Clin. Invest. 1993;92:1349.
Wang, T.C., and Brand, S.J. Islet cell-specific regulatory domain in the gastrin promoter contains adjacent positive and negative DNA elements. J. Biol. Chem. 1990;265:8908.
Rorsmam, P., Arkhammer, P., Bokvist, K., Hellerstrom, C., Nilsson, T., Welsh, M., Welsh, N., and Berggren, P. Failure of glucose to elicit a normal secretory response in fetal pancreatic beta cells results from glucose insensitivity of the ATP-regulated K+ channels. Proc. Nat’l. Acad. Sci. USA 1989;86:4505.
Yamanaka, Y, Friess, H., Buchler, M., Beger, H.G., Gold, L.I., and Korc, M. Synthesis and expression of transforming growth factor β-1, β-2, and β-3 in the endocrine and exocrine pancreas. Diabetes 1993;42:746.
Logsdon, C.D., Keyes, L., and Beauchamp, R.D. Transforming growth factor-β (TGF-βl) inhibits pancreatic acinar cell growth. Am. J. Physiol. 1992;262:G364.
Mii, S., Ware, A., and Kent, K.C. Transforming growth factor-beta inhibits human vascular smooth muscle cell growth and migration. Surgery 1993; 1145:464.
Majack, P.A. Beta-type transfroming growth factor specifies organizational behavior in vascular smooth cell cultures. J. Cell Biol. 1987;105:965.
Parekh, T., Saxena, B., Reibman, J., Cronstein, B.N., and Gold, L.I. Neutrophil chemotaxis in response to TGF-β isoforms (TGF-β1, TGF-P2, TGF-P3) is mediated by fibronectin. J. Immunol. 1993; 151:1147.
Otonkoski, T., Beattie, G.M., Rubin, J.S., Lopez, A.D., Baird, A., and Hayek, A. Hepatocyte growth factor/scatter factor has insulinotropic activity in human fetal pancreatic dells. Diabetes 1994;43:947.
Swenne, I., Hill, D.J., Strain, A.J., and Milner, R.D.G. Growth hormone regulation of somatomedin C/insulin-like growth factor I production and DNA replication in fetal rat islets in tissue culture. Diabetes M987;36:288.
Otonkoski, T., Knip, M., Wong, I., and Simell, O. Effects of growth hormone and insulin-like growth factor I on endocrine function of human fetal-like cell clusters during long-term tissue culture. Diabetes 1988;37:1678.
Sandler, S., Anderson, A., Korsgren, O. et al. Tissue culture of human fetal pancreas: effects of nicotinamide on insulin production and formation of isletlike cell clusters. Diabetes 1989;38(suppl 1): 168.
Otonkoski, T., Beattie, G.M., Mally, M.I., Ricordi, C., and Hayek, A. Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells. J. Clin. Invest. 1993;92:1459.
Welsh, M., Mares, J., Oberg, C., and Karlsson, T. Genetic factors of importance for β-cell proliferation. Diabetes/Metab Rev. 1993;9(1):25.
Welsh, M., Welsh, N., Nilsson, T., Arkhammar, R, Pepinsky, R.B., Steiner, D.F., and Berggren, P. Stimulation of pancreatic islet beta-cell replication by oncogenes. Proc. Nat’l. Acad. Sci. USA 1988;85:116.
Welsh M., Claesson-Welsh, L., Hallberg, A., Welsh, N., Betsholtz, C., Arkhammar, P., Nilsson, T., Heldin, C., and Berggren, P. Coexpression of the platelet-derived growth factor (PDGF) B chain and the PDGF β receptor in isolated pancreatic islet cells stimulates DNA synthesis. Proc. Nat’l. Acad. Sci. USA 1990;87:5807.
Welsh, M., and Andersson, A. Transplantation of transfected pancreatic islets: stimulation of β cell DNA synthesis by the src oncogene. Transplantation 1994;57:297.
Varmus, H. Retroviruses. Science 1988;240:1427.
Donahue, R.E., Kessler, S.W., Bodine, D., McDonagh, K., Dunbar, C., Goodman, S., Agricola, B., Byrne, E., Raffeld, M., Moen, R., Bocher, J., Zsebo, K.M., and Neinhaus, A.W. Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. J. Exp. Med. 1992;176:1125.
Graham, F.L., and Prevec, L. Manipulations of adenovirus. In: methods in Molecular Biology, Murray, E.J. ed. The Humanna Press, Inc., Clifton, NJ. 1991;7:109.
Statfor-Perricaudet, L.D., Levrero, M., Chasse, J.F., Perricaudet, M., and Briaud, P. Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. Human Gene Therapy 1990; 1:241.
Gomez-Foix, A.M., Coats, W.S., Baque, S., Alam, T., Gerard, R.D., and Newgard, C.B. Adenovirus mediated transfer of the muscle glycogen phosphorylase gene in hepatocytes confers altered regulation of glycogen metabolism. J. Biol. Chem. 1992;267:25129.
Yang, Y., Ertl, H.C.J., and Wilson, J.M. MHC class I restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with El-deleted recombinant adenovirus. Immunity. 1994; 1:433.
Simon, R.H., Engelhardt, J.F., Yang, Y, Zepeda, N., Weber-Pendleton, s., Grossman, M., and Wilson, J.M. Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study. Hum. Gene. Ther. 1993;4:771.
Herz, J., and Gerard, R.D. Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice. Proc. Nat’l. Acad. Sci. USA 1993;90:2812.
Engelhardt, J.F., Ye, X., Doranz, B., and Wilson, J.M. Ablation of E2a in recombinant adenoviruses improves transgene persistence and decreases imflammatory response in mouse liver. Proc. Nat’l. Acad. Sci. USA 1994;91:6196.
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Hullett, D.A., MacKenzie, D.A., Alam, T., Sollinger, H.W. (1995). Preparation of Fetal Islets for Transplantation: Importance of Growth Factors. In: Peterson, C.M., Jovanovic-Peterson, L., Formby, B. (eds) Fetal Islet Transplantation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1981-2_3
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DOI: https://doi.org/10.1007/978-1-4615-1981-2_3
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