PROGRESS IN ISOLATION AND PURIFICATION OF PORCINE ISLETS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHU Haitao , YU Liang , WANG Bo.

Department of Hepatobiliary, the First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an Shaanxi, 710061, P.R.China. Corresponding author: WANG Bo, E-mail: bobwang75@sina.com;

Corresponding author：

Keywords：

Islets Isolation; Purification; Xenograft; Porcine

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Objective To review the common methods of isolation and purification of porcine islets and research progress. Methods Domestic and abroad literature concerning the isolation and purification of porcine islets was reviewed and analyzed thoroughly. Results The efficacy of the isolation and purification depends on the selection of donor, the procurement and cryopreservation of high-quality donor pancreas, and the selection and improvement of the operation. Conclusion The shortage of transplanted islets could be resolved by the establishment of standardized and optimal process, which may also promote the development of porcine islet xenograft.

Citation： ZHU Haitao,YU Liang,WANG Bo.. PROGRESS IN ISOLATION AND PURIFICATION OF PORCINE ISLETS. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(8): 1012-1016. doi: Copy

1.	Kobayashi N. The current status of islet transplantation and its perspectives. Rev Diabet Stud, 2008, 5(3): 136-143.
2.	Noguchi H. Pancreatic islet transplantation. World J Gastrointest Surg, 2009, 1(1): 16-20.
3.	赵勇. 异种移植免疫学. 北京: 中国医药科技出版社, 2003: 141-189.
4.	Marigliano M, Bertera S, Grupillo M, et al. Pig-to-nonhuman primates pancreatic islet xenotransplantation: an overview. Curr Diab Rep, 2011, 11(5): 402-412.
5.	Hardikar AA, Wang XY, Williams LJ, et al. Functional maturation of fetal porcine β-cells by glucagon-like peptide 1 and cholecystokinin. Endocrinology, 2002, 143(9): 3505-3514.
6.	Dufrane D, Gianello P. Pig islets for clinical islet xenotransplantation. Curr Opin Nephrol Hypertens, 2009, 18(6): 495-500.
7.	Bennet W, Björkland A, Sundberg B, et al. A comparison of fetal and adult porcine islets with regard to Gal alpha (1, 3)Gal expression and the role of human immunoglobulins and complement in islet cell cytotoxicity. Transplantation, 2000, 69(8): 1711-1117.
8.	Groth CG, Korsgren O, Tibell A, et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet, 1994, 344(8934): 1402-1404.
9.	Cardona K, Korbutt GS, Milas Z, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med, 2006, 12(3): 304-306.
10.	Bottino R, Balamurugan AN, Smetanka C, et al. Isolation outcome and functional characteristics of young and adult pig pancreatic islets for transplantation studies. Xenotransplantation, 2007, 14(1): 74-82.
11.	Dufrane D, D’hoore W, Goebbels RM, et al. Parameters favouring successful adult pig islet isolations for xenotransplantation in pig-to-primate models. Xenotransplantation, 2006, 13(3): 204-214.
12.	Rood PP, Buhler LH, Bottino R, et al. Pig-to-nonhuman primate islet xenotransplantation: a review of current problems. Cell Transplant, 2006, 15(2): 89-104.
13.	Dufrane D, Goebbels RM, Fdilat I, et al. Impact of porcine islet size on cellular structure and engraftment after transplantation: adult versus young pigs. Pancreas, 2005, 30(2): 138-147.
14.	Kim HI, Lee SY, Jin SM, et al. Parameters for successful pig islet isolation as determined using 68 specific-pathogen-free miniature pigs. Xenotransplantation, 2009, 16(1): 11-18.
15.	Kim JH, Kim HI, Lee KW, et al. Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs. Xenotransplantation, 2007, 14(1): 60-66.
16.	蒋小峰, 钱滔来, 向广阳, 等. 五指山小型猪胰岛分离和纯化的初步研究. 临床医学工程, 2011, 18(9): 1343-1347.
17.	Anazawa T, Balamurugan AN, Matsumoto S, et al. Rapid quantitative assessment of the pig pancreas biopsy predicts islet yield. Transplant Proc, 2010, 42(6): 2036-2039.
18.	Jin SM, Shin JS, Kim KS, et al. Islet isolation from adult designated pathogen-free pigs: use of the newer bovine nervous tissue-free enzymes and a revised donor selection strategy would improve the islet graft function. Xenotransplantation, 2011, 18(6): 369-379.
19.	van der Windt DJ, Bottino R, Casu A, et al. Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am J Transplant, 2009, 9(12): 2716-2726.
20.	d’Apice AJ, Cowan PJ. Gene-modified pigs. Xenotransplantation, 2008, 15(2): 87-90.
21.	Ekser B, Cooper DK. Overcoming the barriers to xenotransplantation: prospects for the future. Expert Rev Clin Immunol, 2010, 6(2): 219-230.
22.	Le Bas-Bernardet S, Tillou X, Poirier N, et al. Xenotransplantation of galactosyl-transferase knockout, CD55, CD59, CD39, and fucosyl-transferase transgenic pig kidneys into baboons. Transplant Proc, 2011, 43(9): 3426-3430.
23.	Goto M, Imura T, Inagaki A, et al. The impact of ischemic stress on the quality of isolated pancreatic islets. Transplant Proc, 2010, 42(6): 2040-2042.
24.	张明, 杜成友. 不同热缺血时间对猪胰岛获取及功能的影响. 中国组织工程研究与临床康复, 2011, 15(5): 847-850.
25.	Kuroda Y, Fujino Y, Morita A, et al. Oxygenation of the human pancreas during preservation by a two-layer (University of Wisconsin solution/perfluorochemical) cold-storage method. Transplantation, 1992, 54(3): 561-562.
26.	Gioviale MC, Damiano G, Palumbo VD, et al. Pancreatic islets from non-heart-beating donor pig: two-layer preservation method in an in vitro porcine model. Int J Artif Organs, 2011, 34(6): 519-525.
27.	Brandhorst D, Iken M, Brendel MD, et al. Adaption of neutral protease activity for islet isolation from the long-term two-layer method-stored pig pancreas. Transplant Proc, 2005, 37(1): 458-459.
28.	Noguchi H, Ueda M, Nakai Y, et al. Modified two-layer preservation method (M-Kyoto/PFC) improves islet yields in islet isolation. Am J Transplant, 2006, 6(3): 496-504.
29.	Brandhorst D, Iken M, Brendel MD, et al. Long-term preservation of the pig pancreas by a one-layer method for successful islet isolation. Transplant Proc, 2005, 37(1): 229-230.
30.	Taylor MJ, Baicu S, Greene E, et al. Islet isolation from juvenile porcine pancreas after 24-h hypothermic machine perfusion preservation. Cell Transplant, 2010, 19(5): 613-628.
31.	王珏, 侯宗柳, 李汝红. 半自动纯化法分离纯化成年猪胰岛细胞的实验研究. 昆明医学院学报, 2011, 32(10): 14-18.
32.	Yonekawa Y, Matsumoto S, Okitsu T, et al. Effective islet isolation method with extremely high islet yields from adult pigs. Cell Transplant, 2005, 14(10): 757-762.
33.	Gray DW, Sudhakaran N, Titus TT, et al. Development of a novel digestion chamber for human and porcine islet isolation. Transplant Proc, 2004, 36(4): 1135-1138.
34.	Kim SC, Han DJ, Kang CH, et al. Experimental islet isolation in porcine pancreas with new enzyme Liberase PI. Transplant Proc, 2004, 36(7): 2197-2199.
35.	Bucher P, Bosco D, Mathe Z, et al. Optimization of neutral protease to collagenase activity ratio for islet of Langerhans isolation. Transplant Proc, 2004, 36(4): 1145-1146.
36.	Brandhorst D, Huettler S, Alt A, et al. Adjustment of the ratio between collagenase class II and I improves islet isolation outcome. Transplant Proc, 2005, 37(8): 3450-3451.
37.	Brandhorst H, Alt A, Huettler S, et al. The ratio between class II and class I collagenase determines the amount of neutral protease activity required for efficient islet release from the rat pancreas. Transplant Proc, 2005, 37(1): 215-216.
38.	Hilling DE, Rijkelijkhuizen JK, Töns HA, et al. Porcine islet isolation outcome is not affected by the amount and distribution of collagen in the pancreas. Xenotransplantation, 2010, 17(3): 250-255.
39.	Kinasiewicz A, Juszczak M, Pachecka J, et al. Pancreatic islets isolation using different protocols with in situ flushing and intraductal collagenase injection. Physiol Res, 2004, 53(3): 327-333.
40.	Andrades P, Asiedu C, Ray P, et al. Islet yield after different methods of pancreatic liberase delivery. Transplant Proc, 2007, 39(1): 183-184.
41.	Szot GL, Koudria P, Bluestone JA. Murine pancreatic islet isolation. J Vis Exp, 2007, (7): 255.
42.	Atwater I, Guajardo M, Caviedes P, et al. Isolation of viable porcine islets by selective osmotic shock without enzymatic digestion. Transplant Proc, 2010, 42(1): 381-386.
43.	张伟杰, Schre J. 成年猪胰岛的分离与纯化. 中华器官移植杂志, 2000, 21(6): 341-343.
44.	Qiao AY, Zhang WH, Chen XJ, et al. Isolation and purification of islet cells from adult pigs. Transplant Proc, 2010, 42(5): 1830-1834.
45.	徐艳艳, 傅红兴, 王浙明, 等. 大鼠胰岛分离纯化技术的改良及活性研究. 中国修复重建外科杂志, 2010, 24(4): 406-409.
46.	杨学伟, 章乐虹, 胡以则, 等. 成年猪胰岛细胞的分离纯化及其微囊包裹. 武汉大学学报: 医学版, 2007, 28(7): 496-499.
47.	李鹏, 李汝红, 赵维山, 等. 云南小耳猪胰岛细胞的分离和纯化方法. 昆明医学院学报, 2009, 30(12): 38-40.
48.	Eckhardt T, Jahr H, Federlin K, et al. Endotoxin impairs the engraftment of rat islets transplanted beneath the kidney capsule of C57BL/6-mice. J Mol Med (Berl), 1999, 77(1): 123-125.
49.	张桦, 陈宏, 张振, 等. 碘克沙醇及Ficoll-400分离纯化大鼠胰岛细胞的效果对比. 世界华人消化杂志, 2007, 15(15): 1759-1762.
50.	黄跃南, 郭欣, 田素礼, 等. 成年猪胰岛分离纯化方法的改良. 世界华人消化杂志, 2005, 13(15): 1912-1914.
51.	Min T, Yi L, Chao Z, et al. Superiority of visipaque (iodixanol)-controlled density gradient over Ficoll-400 in adult porcine islet purification. Transplant Proc, 2010, 42(5): 1825-1829.
52.	杨卿尧, 田郁文. 胰岛细胞移植. 台湾医学, 2007, 11(1): 42-46.
53.	Shawl AI, Park KH, Kim UH. Insulin receptor signaling for the proliferation of pancreatic β-cells: involvement of Ca2+ second messengers, IP3, NAADP and cADPR. Islets, 2009, 1(3): 216-223.
54.	Dekki N, Nilsson R, Norgren S, et al. Type 1 diabetic serum interferes with pancreatic beta-cell Ca2+-handling. Biosci Rep, 2007, 27(6): 321-326.
55.	Corbin KL, Hall TE, Haile R, et al. A novel fluorescence imaging approach for comparative measurements of pancreatic islet function in vitro. Islets, 2011, 3(1): 14-20.
56.	Elliott RB. Towards xenotransplantation of pig islets in the clinic. Curr Opin Organ Transplant, 2011, 16(2): 195-200.

1. Kobayashi N. The current status of islet transplantation and its perspectives. Rev Diabet Stud, 2008, 5(3): 136-143.
2. Noguchi H. Pancreatic islet transplantation. World J Gastrointest Surg, 2009, 1(1): 16-20.
3. 赵勇. 异种移植免疫学. 北京: 中国医药科技出版社, 2003: 141-189.
4. Marigliano M, Bertera S, Grupillo M, et al. Pig-to-nonhuman primates pancreatic islet xenotransplantation: an overview. Curr Diab Rep, 2011, 11(5): 402-412.
5. Hardikar AA, Wang XY, Williams LJ, et al. Functional maturation of fetal porcine β-cells by glucagon-like peptide 1 and cholecystokinin. Endocrinology, 2002, 143(9): 3505-3514.
6. Dufrane D, Gianello P. Pig islets for clinical islet xenotransplantation. Curr Opin Nephrol Hypertens, 2009, 18(6): 495-500.
7. Bennet W, Björkland A, Sundberg B, et al. A comparison of fetal and adult porcine islets with regard to Gal alpha (1, 3)Gal expression and the role of human immunoglobulins and complement in islet cell cytotoxicity. Transplantation, 2000, 69(8): 1711-1117.
8. Groth CG, Korsgren O, Tibell A, et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet, 1994, 344(8934): 1402-1404.
9. Cardona K, Korbutt GS, Milas Z, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med, 2006, 12(3): 304-306.
10. Bottino R, Balamurugan AN, Smetanka C, et al. Isolation outcome and functional characteristics of young and adult pig pancreatic islets for transplantation studies. Xenotransplantation, 2007, 14(1): 74-82.
11. Dufrane D, D’hoore W, Goebbels RM, et al. Parameters favouring successful adult pig islet isolations for xenotransplantation in pig-to-primate models. Xenotransplantation, 2006, 13(3): 204-214.
12. Rood PP, Buhler LH, Bottino R, et al. Pig-to-nonhuman primate islet xenotransplantation: a review of current problems. Cell Transplant, 2006, 15(2): 89-104.
13. Dufrane D, Goebbels RM, Fdilat I, et al. Impact of porcine islet size on cellular structure and engraftment after transplantation: adult versus young pigs. Pancreas, 2005, 30(2): 138-147.
14. Kim HI, Lee SY, Jin SM, et al. Parameters for successful pig islet isolation as determined using 68 specific-pathogen-free miniature pigs. Xenotransplantation, 2009, 16(1): 11-18.
15. Kim JH, Kim HI, Lee KW, et al. Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs. Xenotransplantation, 2007, 14(1): 60-66.
16. 蒋小峰, 钱滔来, 向广阳, 等. 五指山小型猪胰岛分离和纯化的初步研究. 临床医学工程, 2011, 18(9): 1343-1347.
17. Anazawa T, Balamurugan AN, Matsumoto S, et al. Rapid quantitative assessment of the pig pancreas biopsy predicts islet yield. Transplant Proc, 2010, 42(6): 2036-2039.
18. Jin SM, Shin JS, Kim KS, et al. Islet isolation from adult designated pathogen-free pigs: use of the newer bovine nervous tissue-free enzymes and a revised donor selection strategy would improve the islet graft function. Xenotransplantation, 2011, 18(6): 369-379.
19. van der Windt DJ, Bottino R, Casu A, et al. Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am J Transplant, 2009, 9(12): 2716-2726.
20. d’Apice AJ, Cowan PJ. Gene-modified pigs. Xenotransplantation, 2008, 15(2): 87-90.
21. Ekser B, Cooper DK. Overcoming the barriers to xenotransplantation: prospects for the future. Expert Rev Clin Immunol, 2010, 6(2): 219-230.
22. Le Bas-Bernardet S, Tillou X, Poirier N, et al. Xenotransplantation of galactosyl-transferase knockout, CD55, CD59, CD39, and fucosyl-transferase transgenic pig kidneys into baboons. Transplant Proc, 2011, 43(9): 3426-3430.
23. Goto M, Imura T, Inagaki A, et al. The impact of ischemic stress on the quality of isolated pancreatic islets. Transplant Proc, 2010, 42(6): 2040-2042.
24. 张明, 杜成友. 不同热缺血时间对猪胰岛获取及功能的影响. 中国组织工程研究与临床康复, 2011, 15(5): 847-850.
25. Kuroda Y, Fujino Y, Morita A, et al. Oxygenation of the human pancreas during preservation by a two-layer (University of Wisconsin solution/perfluorochemical) cold-storage method. Transplantation, 1992, 54(3): 561-562.
26. Gioviale MC, Damiano G, Palumbo VD, et al. Pancreatic islets from non-heart-beating donor pig: two-layer preservation method in an in vitro porcine model. Int J Artif Organs, 2011, 34(6): 519-525.
27. Brandhorst D, Iken M, Brendel MD, et al. Adaption of neutral protease activity for islet isolation from the long-term two-layer method-stored pig pancreas. Transplant Proc, 2005, 37(1): 458-459.
28. Noguchi H, Ueda M, Nakai Y, et al. Modified two-layer preservation method (M-Kyoto/PFC) improves islet yields in islet isolation. Am J Transplant, 2006, 6(3): 496-504.
29. Brandhorst D, Iken M, Brendel MD, et al. Long-term preservation of the pig pancreas by a one-layer method for successful islet isolation. Transplant Proc, 2005, 37(1): 229-230.
30. Taylor MJ, Baicu S, Greene E, et al. Islet isolation from juvenile porcine pancreas after 24-h hypothermic machine perfusion preservation. Cell Transplant, 2010, 19(5): 613-628.
31. 王珏, 侯宗柳, 李汝红. 半自动纯化法分离纯化成年猪胰岛细胞的实验研究. 昆明医学院学报, 2011, 32(10): 14-18.
32. Yonekawa Y, Matsumoto S, Okitsu T, et al. Effective islet isolation method with extremely high islet yields from adult pigs. Cell Transplant, 2005, 14(10): 757-762.
33. Gray DW, Sudhakaran N, Titus TT, et al. Development of a novel digestion chamber for human and porcine islet isolation. Transplant Proc, 2004, 36(4): 1135-1138.
34. Kim SC, Han DJ, Kang CH, et al. Experimental islet isolation in porcine pancreas with new enzyme Liberase PI. Transplant Proc, 2004, 36(7): 2197-2199.
35. Bucher P, Bosco D, Mathe Z, et al. Optimization of neutral protease to collagenase activity ratio for islet of Langerhans isolation. Transplant Proc, 2004, 36(4): 1145-1146.
36. Brandhorst D, Huettler S, Alt A, et al. Adjustment of the ratio between collagenase class II and I improves islet isolation outcome. Transplant Proc, 2005, 37(8): 3450-3451.
37. Brandhorst H, Alt A, Huettler S, et al. The ratio between class II and class I collagenase determines the amount of neutral protease activity required for efficient islet release from the rat pancreas. Transplant Proc, 2005, 37(1): 215-216.
38. Hilling DE, Rijkelijkhuizen JK, Töns HA, et al. Porcine islet isolation outcome is not affected by the amount and distribution of collagen in the pancreas. Xenotransplantation, 2010, 17(3): 250-255.
39. Kinasiewicz A, Juszczak M, Pachecka J, et al. Pancreatic islets isolation using different protocols with in situ flushing and intraductal collagenase injection. Physiol Res, 2004, 53(3): 327-333.
40. Andrades P, Asiedu C, Ray P, et al. Islet yield after different methods of pancreatic liberase delivery. Transplant Proc, 2007, 39(1): 183-184.
41. Szot GL, Koudria P, Bluestone JA. Murine pancreatic islet isolation. J Vis Exp, 2007, (7): 255.
42. Atwater I, Guajardo M, Caviedes P, et al. Isolation of viable porcine islets by selective osmotic shock without enzymatic digestion. Transplant Proc, 2010, 42(1): 381-386.
43. 张伟杰, Schre J. 成年猪胰岛的分离与纯化. 中华器官移植杂志, 2000, 21(6): 341-343.
44. Qiao AY, Zhang WH, Chen XJ, et al. Isolation and purification of islet cells from adult pigs. Transplant Proc, 2010, 42(5): 1830-1834.
45. 徐艳艳, 傅红兴, 王浙明, 等. 大鼠胰岛分离纯化技术的改良及活性研究. 中国修复重建外科杂志, 2010, 24(4): 406-409.
46. 杨学伟, 章乐虹, 胡以则, 等. 成年猪胰岛细胞的分离纯化及其微囊包裹. 武汉大学学报: 医学版, 2007, 28(7): 496-499.
47. 李鹏, 李汝红, 赵维山, 等. 云南小耳猪胰岛细胞的分离和纯化方法. 昆明医学院学报, 2009, 30(12): 38-40.
48. Eckhardt T, Jahr H, Federlin K, et al. Endotoxin impairs the engraftment of rat islets transplanted beneath the kidney capsule of C57BL/6-mice. J Mol Med (Berl), 1999, 77(1): 123-125.
49. 张桦, 陈宏, 张振, 等. 碘克沙醇及Ficoll-400分离纯化大鼠胰岛细胞的效果对比. 世界华人消化杂志, 2007, 15(15): 1759-1762.
50. 黄跃南, 郭欣, 田素礼, 等. 成年猪胰岛分离纯化方法的改良. 世界华人消化杂志, 2005, 13(15): 1912-1914.
51. Min T, Yi L, Chao Z, et al. Superiority of visipaque (iodixanol)-controlled density gradient over Ficoll-400 in adult porcine islet purification. Transplant Proc, 2010, 42(5): 1825-1829.
52. 杨卿尧, 田郁文. 胰岛细胞移植. 台湾医学, 2007, 11(1): 42-46.
53. Shawl AI, Park KH, Kim UH. Insulin receptor signaling for the proliferation of pancreatic β-cells: involvement of Ca2+ second messengers, IP3, NAADP and cADPR. Islets, 2009, 1(3): 216-223.
54. Dekki N, Nilsson R, Norgren S, et al. Type 1 diabetic serum interferes with pancreatic beta-cell Ca2+-handling. Biosci Rep, 2007, 27(6): 321-326.
55. Corbin KL, Hall TE, Haile R, et al. A novel fluorescence imaging approach for comparative measurements of pancreatic islet function in vitro. Islets, 2011, 3(1): 14-20.
56. Elliott RB. Towards xenotransplantation of pig islets in the clinic. Curr Opin Organ Transplant, 2011, 16(2): 195-200.

Chinese Journal of Reparative and Reconstructive Surgery

PROGRESS IN ISOLATION AND PURIFICATION OF PORCINE ISLETS

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