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Viability and Functions of Alginate-microencapsulated Islets Isolated from Neonatal Pigs
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 Title & Authors
Viability and Functions of Alginate-microencapsulated Islets Isolated from Neonatal Pigs
Lin, Yi-Juain; Wang, Jui-Ping; Chung, Yu-Tung; Sun, Yu-Ling; Chou, Yu-Chi;
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 Abstract
Patients with Type I diabetes mellitus have been treated with porcine insulin for several decades and pigs have recently been deemed an ideal source of microencapsulated islet cells for clinical xenotransplantation. In this study, neonatal pigs were anesthetized and sacrificed prior to a pancreatectomy. Islet cells were isolated from pancreas via collagenase digestion. Islet cells were separated and collected by hand under microscopic guidance. These cells were suspended in 1.4% sodium alginate solution and encapsulated by dropping them into 1.1% calcium chloride solution and in which the round gel in size was 250-400 in diameter. Viability of the microencapsulated islet cells cultured in medium at was assessed by MTT assay. Furthermore, insulin released in response to glucose challenge was investigated using an enzyme-linked immunosorbent assay. Secretion of insulin was low in response to the basal glucose solution (4.4 mM) in medium and was significantly higher in response to the high glucose solution (16.7 mM). The viability of microencapsulated islet cells did not differ significantly over a period of 7 days; that is, the increasing pattern of insulin concentration in the culture medium after glucose stimulation interval day was similar throughout the 7 days cultivation. In summary, experimental evidences indicated that the effects of alginate-microencapsulation prolonged survival of the neonatal porcine islets in vitro cultures and the insulin response to glucose of the islets was maintained.
 Keywords
Neonatal Pig;Islet;Microencapsulation;Insulin;Insulin Secretory Responsiveness;
 Language
English
 Cited by
 References
1.
Archer, F. J. 1983. Monolayer culture of neonatal pig pancreatic islet cells. Diabetologia 24:185-190.

2.
Balamurugan, A. N., B. Ramakrishna and S. Gunasekaran. 2004. Insulin secretory characteristics of monkey pancreatic islets: a simple method of islet isolation and the effect of various density gradients on separation. Diabetes Res. Clin. Pract. 66:13-21. crossref(new window)

3.
Beattie, G. M., J. S. Rubin, M. I. Mally, T. Otonkoski and A. Hayek. 1996. Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact. Diabetes 45:1223-1228. crossref(new window)

4.
Bonner-Weir, S., M. Taneja, G. C. Weir, K. Tatarkiewicz, K. H. Song, A. Sharma and J. J. O'Neil. 2000. In vitro cultivation of human islets from expanded ductal tissue. Proc. Natl. Acad. Sci. USA 97:7999-8004. crossref(new window)

5.
Brit, L. D., P. C. Stojeba, C. R. Scharp, M. H. Greider and D. W. Scharp. 1981. Neonatal pig psuedo-islets. A product of selective aggregation. Diabetes 30:580-583. crossref(new window)

6.
Brunicardi, F. C. and Y. Mullen. 1994. Issues in clinical islet transplantation. Pancreas 9:281-290. crossref(new window)

7.
Cardona, K., G. S. Korbutt, Z. Milas, J. Lyon, J. Cano, W. Jiang, H. Bello-Laborn, B. Hacquoil, E. Strobert, S. Gangappa, C. J. Weber, T. C. Pearson, R. V. Rajotte and C. P. Larsen. 2006. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat. Med. 12:304-306. crossref(new window)

8.
Diabetes Control and Complications Trial Research Group. 1993. The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin dependent diabetes mellitus. New Eng. J. Med. 329:977-986. crossref(new window)

9.
Elliott, R. B., L. Escobar, R. Calafiore, G. Basta, O. Garkavenko, A. Vasconcellos and C. Bambra. 2005. Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys. Transplan. Proc. 37:466-469. crossref(new window)

10.
Elliott, R. B., L. Escobar, P. L. J. Tan, O. Garkavenko, R. Calafiore, P. Basta, A. V. Vasconcellos, D. F. Emerich, C. Thanos and C. Bambra. 2005. Intraperitoneal alginate-encapsulated neonatal porcine islets in a placebo-controlled study with 16 diabetic cynomolgus primates. Transplan. Proc. 37:3505-3508. crossref(new window)

11.
Garfinkel, M. R., R. C. Harland and E. C. Opara. 1998. Optimization of the microencapsulated islet for transplantation. J. Surg. Res. 76:7-10. crossref(new window)

12.
Han, S. E., H. G. Lee, C. H. Yun, Z. S. Hong, S. H. Kim, S. K. Kang, S. H. Kim, J. S. Cho, S. H. Ha and Y. J. Choi. 2005. Effect of cellular zinc on the regulation of C2-ceramide induced apoptosis in mammary epithelial and macrophage cell lines. Asian-Aust. J. Anim. Sci. 18:1741-1745.

13.
Heald, K. A., T. R. Jay, D. Topham, J. Webberley and R. Downing. 1996. The effect of gnotobiotic rearing on porcine islet isolation and function. Transplan. Proc. 28:824-825.

14.
Kin, T., G. S. Korbutt, T. Kobayashi and J. M. Dufour. 2005. Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets. Diabetes 54:1032-1039. crossref(new window)

15.
Kin, T., H. Iwata, Y. Aomatsu, T. Ohyama, H. Kanehiro, M. Hisanaga and Y. Nakajima. 2002. Xenotransplantation of pig islets in diabetic dogs with use of a microcapsule composed of agarose and polystyrene sulfonic acid mixed gel. Pancreas 25:94-100. crossref(new window)

16.
Korbutt, G. S., J. F. Elliott, Z. Ao, D. K. Smith, G. L. Warnock and R. V. Rajotte. 1996. Large scale isolation, growth, and function of porcine neonatal islet cells. J. Clin. Investig. 97:2119-2129. crossref(new window)

17.
Korbutt, G. S., A. G. Mallett, Z. Ao, M. Flashne and R. V. Rajotte. 2004. Improved survival of microencapsulated islets during in vitro culture and enhanced metabolic function following Transplantation. Diabetologia 47:1810-1818. crossref(new window)

18.
Krickhahn, M., C. Buhler, T. Meyer, A. Thiede and K. Ulrichs. 2002. The morphology of islets within the porcine donor pancreas determines the isolation result: successful isolation of pancreatic islets can now be achieved from young market pigs. Cell Transplan. 11:827-838.

19.
Lacy, P. E., O. D. Hegre, A. Gerasimidi-Vazeou, F. T. Gentile and K. E. Dionne. 1991. Maintenance of normoglycemia in diabetic mice by subcutaneous xenografts of encapsulated islets. Sci. 254:1782-1784. crossref(new window)

20.
Lim, F. and A. M. Sun. 1980. Microencapsulated islets as a bioartificial endocrine pancreas. Sci. 210:908-910. crossref(new window)

21.
MacKenzie, D. A., D. A. Hullett and H. W. Sollinger. 2003. Xenogeneic transplantation of porcine islets: an overview. Transplant. 76:887-891. crossref(new window)

22.
Marchetti, P., E. H. Finke, A. Gerasimidi-Vazeou, L. Falqui and D. W. Scharp and P. E. Lacy. 1991. Automated large-scale isolation, in vitro function and xenotransplantation of porcine islets of Langerhans. Transplant. 52:209-213. crossref(new window)

23.
Monroy, B., J. Honiger, S. Darquy and G. Reach. 1997. Use of polyethyleneglycol for porcine islet cryopreservation. Cell Transplant. 6:613-621. crossref(new window)

24.
Narang, A. S. and R. I. Mahato. 2006. Biological and biomaterial approaches for improved islet transplantation. Pharmaco. Rev. 58:194-243. crossref(new window)

25.
Opara, E. C., V. S. Hubbard, W. M. Burch and O. E. Akwari. 1992. Characterization of the insulinotropic potency of polyunsaturated fatty acids. Endocrinol. 130:657-662. crossref(new window)

26.
Panza, J. L., W. R. Wagner, H. L. Rilo, R. H. Rao, E. J. Beckman and A. J. Russell. 2000. Treatment of rat pancreatic islets with reactive PEG. Biomaterials 21:1155-1164. crossref(new window)

27.
Rayat, G. R., R. V. Rajotte and G. S. Korbutt. 1999. Potential application of neonatal porcine islets as treatment for type 1 diabetes: a review. Ann. N. Y. Acad. Sci. 875:175-188. crossref(new window)

28.
Rayat, G. R., R. V. Rajotte, Z. Ao and G. S. Korbutt. 2000. Microencapsulation of neonatal porcine islets: Protection from human antibody/complement-mediated cytolysis in vitro and long-term reversal of diabetes in nude mice. Transplant. 69:1084-1090. crossref(new window)

29.
Ricordi, C., D. W. Gray, B. J. Hering, D. B. Kaufman, G. L. Warnock, N. M. Kneteman, S. P. Lake, N. J. London, C. Socci and R. Alejandro. 1990. Islet isolation assessment in man and large animals. Acta Diabetol. Lat. 27:185-195. crossref(new window)

30.
Ryan, E. A., J. R. T. Lakey, B. Paty, S. Imes, G. S. Korbutt, N. M. Kneteman, D. Bigam, R. V. Rajotte and A. M. J. Shapiro. 2002. Successful islet transplantation: Continued insulin reserve provides long term glycemic control. Diabetes 51:2148-2157. crossref(new window)

31.
Ryan, E. A., J. R. T. Lakey, R. V. Rajotte, G. S. Korbutt, T. Kin, S. Imes, A. Rabinovitch, J. F. Elliot, D. Bigam, N. M. Kneteman, G. L. Warnock, I. Larsen and A. M. J. Shapiro. 2001. Clinical outcomes and insulin secretion after islet transplantation with the Edmonton Protocol. Diabetes 50:710-719. crossref(new window)

32.
Schaffellner, S., V. Stadlbauer, P. Stiegler, O. Hauser, G. Halwachs, C. Lackner, F. Iberer and K. H. Tscheliessnigg. 2005. Porcine islet cells microencapsulated in sodium cellulose sulfate. Transplant. Proc. 37:248-252. crossref(new window)

33.
Shapiro, A. M. J., J. R. T. Lakey, E. A. Ryan, G. S. Korbutt, E. Toth, G. L. Warnock, N. M. Kneteman and R. V. Rajotte. 2000. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid free immunosuppressive regimen. New England J. Med. 343:230-238. crossref(new window)

34.
Trivedi, N., J. Hollister-Lock, M. D. Lopez-Avalos, J. J. O'Neil, M. Keegan, S. Bonner-Weir and G. C. Weir. 2001. Increase in $\beta$- cell mass in transplanted porcine neonatal pancreatic cell clusters is due to proliferation of $\beta$-cells and differentiation of duct cells. Endocrinol. 142:2115-2122. crossref(new window)

35.
Ye, Y., M. Niekrasz, S. Kosanke, R. Welsh, H. E. Jordan, J. C. Fox, W. C. Edwards, C. Maxwell and D. K. Cooper. 1994. The pig as a potential organ donor for man. A study of potentially transferable disease from donor pig to recipient man. Transplant. 57:694-703. crossref(new window)

36.
Yoon, K., R. R. Quickel, K. Tatarkiewicz, T. R. Ulrich, J. Hollister-Lock, N. Trivedi, S. Bonner-Weir and G. C. Weir. 1999. Differentiation and expansion of beta cell mass in porcine neonatal pancreatic cell clusters transplanted into nude mice. Cell Transplan. 8:673-689.

37.
Zhang, C. Y., G. Baffy, P. Perret, S. Krauss, O. Peroni, D. Grujic, T. Hagen, A. J. Vidal-Puig, O. Boss, Y. B. Kim, X. X. Zheng, M. B. Wheeler, G. I. Shulman, C. B. Chan, B. B. Lowell. 2001. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105:745-755. crossref(new window)