胰岛移植最新进展及前景展望

殷浩

doi:10.3969/j.issn.1674-7445.2019.06.008

胰岛移植最新进展及前景展望

doi: 10.3969/j.issn.1674-7445.2019.06.008

殷浩^,

200003 上海，海军军医大学上海长征医院全军器官移植中心

基金项目:

国家自然科学基金面上项目 81870530

上海市科研基金 2018YQ53

上海市科研基金 SHDC12018X14

上海市科研基金 19QA1408600

详细信息

作者简介:
殷浩,医学博士,教授。现任海军军医大学上海长征医院全军器官移植研究所副所长及胰岛移植学科带头人、上海市内分泌质控中心胰岛移植质控组长、上海市黄浦区卫生健康委员会副主任、深圳大学及同济大学附属医院客座教授等。兼任国际移植协会、美国移植外科医师协会、国际胰腺及胰岛移植协会等成员,中国出生缺陷儿童糖尿病防治专家委员会副主任委员,中国医师协会机器人外科医师委员会青年委员,中国研究型医院学会糖尿病专业委员会器官移植与代谢性疾病学组委员等。兼任《器官移植》杂志编委。从事胰岛移植、肝移植临床及基础研究十余年,先后于美国及日本完成博士后和访问学者工作。回国后开展亚洲首例达芬奇机器人全胰切除联合自体胰岛移植、上海市首例DCD胰岛移植、胰岛联合肾脏移植以及儿童胰岛移植,指导多个省市医院完成当地首例胰岛移植,目前完成胰岛移植例数及疗效均位居全国第一。主持参与国家及省部级共10多项科研基金,总科研经费逾1000万元。发表SCI论文数十篇,主编及参编6部专著。

通讯作者:
殷浩，Email：roytina0241032@hotmail.com

中图分类号: R617, R587.1
计量
- 文章访问数: 246
- HTML全文浏览量: 94
- PDF下载量: 35
- 被引次数: 0
出版历程
- 收稿日期: 2019-09-16
- 网络出版日期: 2021-01-19
- 刊出日期: 2019-11-15

The latest research progress and prospect of islet transplantation

Yin Hao^,

摘要

摘要: 近年来, 胰岛移植在治疗糖尿病的研究中取得了巨大进展, 其对于胰岛素依赖型糖尿病、糖尿病合并终末期肾病具有重要的治疗价值, 使患者不再依赖于外源性胰岛素, 且避免相关并发症的发生发展, 从而保护肾脏等重要器官。本文就胰岛移植的发展历史与现状、胰岛移植面对的挑战及应对策略进行介绍。
- 胰岛移植 /
- 糖尿病 /
- 排斥反应 /
- 干细胞 /
- 糖化血红蛋白 /
- 胰岛β细胞

HTML全文

参考文献(58)

[1]	WANG L, GAO P, ZHANG M, et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013[J]. JAMA, 2017, 317(24):2515-2523. DOI: 10.1001/jama.2017.7596.
[2]	BERGENSTAL RM, TAMBORLANE WV, AHMANN A, et al. Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes[J]. N Engl J Med, 2010, 363(4):311-320. DOI: 10.1056/NEJMoa1002853.
[3]	CHATTERJEE S, KHUNTI K, DAVIES MJ. Type 2 diabetes[J]. Lancet, 2017, 389(10085):2239-2251. DOI: 10.1016/S0140-6736(17)30058-2.
[4]	VINER R, WHITE B, CHRISTIE D. Type 2 diabetes in adolescents: a severe phenotype posing major clinical challenges and public health burden[J]. Lancet, 2017, 389(10085):2252-2260. DOI: 10.1016/S0140-6736(17)31371-5.
[5]	KARGES B, BINDER E, ROSENBAUER J. Complications with insulin pump therapy vs insulin injection therapy-reply[J]. JAMA, 2018, 319(5):503-504. DOI: 10.1001/jama.2017.20357.
[6]	SHAH VN. Complications with insulin pump therapy vs insulin injection therapy[J]. JAMA, 2018, 319(5):502-503. DOI: 10.1001/jama.2017.20345.
[7]	BARTON FB, RICKELS MR, ALEJANDRO R, et al. Improvement in outcomes of clinical islet transplantation: 1999-2010[J]. Diabetes Care, 2012, 35(7):1436-1445. DOI: 10.2337/dc12-0063.
[8]	KELLY WD, LILLEHEI RC, MERKEL FK, et al. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy[J]. Surgery, 1967, 61(6):827-837. http://cn.bing.com/academic/profile?id=f5f2d4c18c57381b8a0a71d9fad0db10&encoded=0&v=paper_preview&mkt=zh-cn
[9]	HOWELL SL, KOSTIANOVSKY M, LACY PE. Beta granule formation in isolated islets of langerhans: a study by electron microscopic radioautography[J]. J Cell Biol, 1969, 42(3):695-705. doi: 10.1083/jcb.42.3.695
[10]	SUTHERLAND DE, GORES PF, FARNEY AC, et al. Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota[J]. Am J Surg, 1993, 166(5):456-491. doi: 10.1016/S0002-9610(05)81142-0
[11]	KOLB E, LARGIADÈR F. Clinical islet transplantation[J]. Transplant Proc, 1980, 12(4 Suppl 2):205-207. http://d.old.wanfangdata.com.cn/Periodical/zhqgyz98199101007
[12]	RICORDI C, LACY PE, FINKE EH, et al. Automated method for isolation of human pancreatic islets[J]. Diabetes, 1988, 37(4):413-420. doi: 10.2337/diab.37.4.413
[13]	LAKE SP, BASSETT PD, LARKINS A, et al. Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator[J]. Diabetes, 1989, 38 (Suppl 1):143-145. doi: 10.2337-diabetes.38.2.244/
[14]	SCHARP DW, LACY PE, SANTIAGO JV, et al. Insulin independence after islet transplantation into type Ⅰ diabetic patient[J]. Diabetes, 1990, 39(4):515-518. doi: 10.2337/diab.39.4.515
[15]	The CITR Coordinating Center and Investigators. The collaborative islet transplant registry 2009 annual report[EB/OL]. [2018-03-16]. http://www.citregistry.org/reports/reports.htm.
[16]	SHAPIRO AM, LAKEY JR, RYAN EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen[J]. N Engl J Med, 2000, 343(4):230-238. doi: 10.1056/NEJM200007273430401
[17]	RYAN EA, PATY BW, SENIOR PA, et al. Five-year follow-up after clinical islet transplantation[J]. Diabetes, 2005, 54(7):2060-2069. doi: 10.2337/diabetes.54.7.2060
[18]	QI M, KINZER K, DANIELSON KK, et al. Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience[J]. Acta Diabetol, 2014, 51(5):833-843. DOI: 10.1007/s00592-014-0627-6.
[19]	胡远峰, 张洪, 张洪德, 等.11例胰岛素依赖型糖尿病患者胰岛移植临床研究简报[J].上海医学, 1982, 5(8): 485-486. http://www.cnki.com.cn/Article/CJFDTotal-SHYX198208021.htm HU YF, ZHANG H, ZHANG HD, et al. Clinical study of islet transplantation in 11 patients with insulin-dependent diabetes mellitus[J]. Shanghai Med J, 1982, 5(8):485-486. http://www.cnki.com.cn/Article/CJFDTotal-SHYX198208021.htm
[20]	李大伟, 万初生.我国首例成人胰岛细胞移植获得成功[J].首都医药, 2003, 31(8):17. http://d.old.wanfangdata.com.cn/Periodical/sdyy200308010 LI DW, WAN CS. China' s first adult islet cell transplantation succeeded[J]. Cap Med, 2003, 31(8):17. http://d.old.wanfangdata.com.cn/Periodical/sdyy200308010
[21]	谢平, 穆会君, 徐卓群, 等.成人胰岛细胞的分离纯化及初步的临床应用[J].中华器官移植杂志, 2005, 26(6): 350-352. DOI: 10.3760/cma.j.issn.0254-1785.2005.06.010. XIE P, MU HJ, XU ZQ, et al. Adult pancreatic islet isolation, purification and application in the diabetes patient[J]. Chin J Organ Transplant, 2005, 26(6):350-352. DOI: 10.3760/cma.j.issn.0254-1785.2005.06.010.
[22]	谭建明, 蔡锦全, 杨顺良, 等.肾移植联合成人胰岛细胞移植治疗糖尿病肾病七例报告[J].中华泌尿外科杂志, 2009, 30(3):168-171. DOI:10.3760/cma.j.issn.1000-6702. 2009.03.008. TAN JM, CAI JQ, YANG SL, et al. Simultaneous adult islet-kidney transplantation in 7 patients of type 1 diabetes mellitus with end-stage renal failure[J]. Chin J Urol, 2009, 30(3):168-171. DOI:10.3760/cma.j.issn. 1000-6702.2009.03.008.
[23]	刘永锋, 程颖, 孟一曼, 等.成人胰岛移植治疗2型糖尿病三例[J].中华器官移植杂志, 2011, 32(3):156-158. DOI: 10.3760/cma.j.issn.0254-1785.2011.03.008. LIU YF, CHENG Y, MENG YM, et al. Adult islet transplantation for type 2 diabetes mellitus: 3 cases report[J]. Chin J Organ Transplant, 2011, 32(3):156-158. DOI: 10.3760/cma.j.issn.0254-1785.2011.03.008.
[24]	STEGALL MD, DEAN PG, SUNG R, et al. The rationale for the new deceased donor pancreas allocation schema[J]. Transplantation, 2007, 83(9):1156-1161. doi: 10.1097/01.tp.0000261104.27113.05
[25]	AL-ADRA DP, GILL RS, IMES S, et al. Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus[J]. Transplantation, 2014, 98(9):1007-1012. DOI: 10.1097/TP.0000000000000217.
[26]	MATSUMOTO S, OKITSU T, IWANAGA Y, et al. Insulin independence after living-donor distal pancreatectomy and islet allotransplantation[J]. Lancet, 2005, 365(9471):1642-1644. doi: 10.1016/S0140-6736(05)66383-0
[27]	MATSUMOTO S, OKITSU T, IWANAGA Y, et al. Follow-up study of the first successful living donor islet transplantation[J]. Transplantation, 2006, 82(12):1629-1633. doi: 10.1097/01.tp.0000250547.52725.ff
[28]	ISRANI AK, ZAUN D, ROSENDALE JD, et al. OPTN/SRTR 2012 annual data report: deceased organ donation[J]. Am J Transplant, 2014, 14 (Suppl 1):167-183. DOI: 10.1111/ajt.12585.
[29]	ISRANI AK, SKEANS MA, GUSTAFSON SK, et al. OPTN/SRTR 2012 annual data report: pancreas[J]. Am J Transplant, 2014, 14 (Suppl 1):45-68. DOI: 10.1111/ajt.12580.
[30]	REZANIA A, BRUIN JE, ARORA P, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells[J]. Nat Biotechnol, 2014, 32(11):1121-1133. DOI: 10.1038/nbt.3033.
[31]	TASK FORCE MEMBERS, RYDÉN L, GRANT PJ, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD)[J]. Eur Heart J, 2013, 34(39):3035-3087. DOI: 10.1093/eurheartj/eht108.
[32]	SUN Y, SHI H, YIN S, et al. Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving β-cell destruction[J]. ACS Nano, 2018, 12(8):7613-7628. DOI: 10.1021/acsnano.7b07643.
[33]	CARLSSON PO, SCHWARCZ E, KORSGREN O, et al. Preserved β-cell function in type 1 diabetes by mesenchymal stromal cells[J]. Diabetes, 2015, 64(2):587- 592. DOI: 10.2337/db14-0656.
[34]	LUMELSKY N, BLONDEL O, LAENG P, et al. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets[J]. Science, 2001, 292(5520):1389-1894. doi: 10.1126/science.1058866
[35]	ZHANG D, JIANG W, LIU M, et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells[J]. Cell Res, 2009, 19(4):429-438. DOI: 10.1038/cr.2009.28.
[36]	SHEN J, CHENG Y, HAN Q, et al. Generating insulin-producing cells for diabetic therapy: existing strategies and new development[J]. Ageing Res Rev, 2013, 12(2):469-478. DOI: 10.1016/j.arr.2013.01.001.
[37]	ORTIZ LA, GAMBELLI F, MCBRIDE C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects[J]. Proc Natl Acad Sci U S A, 2003, 100(14):8407-8411. doi: 10.1073/pnas.1432929100
[38]	RAHAVI H, HASHEMI SM, SOLEIMANI M, et al. Adipose tissue-derived mesenchymal stem cells exert in vitro immunomodulatory and beta cell protective functions in streptozotocin-induced diabetic mice model[J]. J Diabetes Res, 2015:878535. DOI: 10.1155/2015/ 878535.
[39]	ZHENG G, GE M, QIU G, et al. Mesenchymal stromal cells affect disease outcomes via macrophage polarization[J]. Stem Cells Int, 2015:989473. DOI: 10.1155/2015/989473.
[40]	BELL GI, BROUGHTON HC, LEVAC KD, et al. Transplanted human bone marrow progenitor subtypes stimulate endogenous islet regeneration and revascularization[J]. Stem Cells Dev, 2012, 21(1):97-109. DOI: 10.1089/scd.2010.0583.
[41]	ITO T, ITAKURA S, TODOROV I, et al. Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function[J]. Transplantation, 2010, 89(12):1438-1445. doi: 10.1097/TP.0b013e3181db09c4
[42]	GROTH CG, KORSGREN O, TIBELL A, et al. Transplantation of porcine fetal pancreas to diabetic patients[J]. Lancet, 1994, 344(8934):1402-1404. doi: 10.1016/S0140-6736(94)90570-3
[43]	王维, 莫朝辉, 叶斌, 等.新生猪胰岛移植治疗糖尿病病人的临床研究[J].中南大学学报(医学版), 2011, 36(12): 1134-1140. DOI: 10.3969/j.issn.1672-7347.2011.12.002. WANG W, MO ZH, YE B, et al. A clinical trial of xenotransplantation of neonatal pig islets for diabetic patients[J]. J Cent South Univ (Med Sci), 2011, 36(12):1134-1140. DOI: 10.3969/j.issn.1672-7347.2011.12.002.
[44]	O' GORMAN D, KIN T, MURDOCH T, et al. The standardization of pancreatic donors for islet isolation[J]. Transplant Proc, 2005, 37(2):1309-1310. doi: 10.1016/j.transproceed.2004.12.087
[45]	WITKOWSKI P, LIU Z, CERNEA S, et al. Validation of the scoring system for standardization of the pancreatic donor for islet isolation as used in a new islet isolation center[J]. Transplant Proc, 2006, 38(9):3039-3040. doi: 10.1016/j.transproceed.2006.08.143
[46]	RICORDI C, GOLDSTEIN JS, BALAMURUGAN AN, et al. National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: manufacture of a complex cellular product at eight processing facilities[J]. Diabetes, 2016, 65(11):3418-3428. doi: 10.2337/db16-0234
[47]	BRENNAN DC, KOPETSKIE HA, SAYRE PH, et al. Long-term follow-up of the edmonton protocol of islet transplantation in the United States[J]. Am J Transplant, 2016, 16(2):509-517. DOI: 10.1111/ajt.13458.
[48]	YOSHIMATSU G, KUNNATHODI F, SARAVANAN PB, et al. Pancreatic β-cell-derived IP-10/CXCL10 isletokine mediates early loss of graft function in islet cell transplantation[J]. Diabetes, 2017, 66(11):2857-2867. DOI: 10.2337/db17-0578.
[49]	EMAMAULLEE JA, SHAPIRO AM. Factors influencing the loss of beta-cell mass in islet transplantation[J]. Cell Transplant, 2007, 16(1):1-8. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=163d30313d4f5d3a71e2eac33c0cfc8a
[50]	EICH T, ERIKSSON O, SUNDIN A, et al. Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model[J]. Transplantation, 2007, 84(7):893-898. doi: 10.1097/01.tp.0000284730.86567.9f
[51]	SAMY KP, DAVIS RP, GAO Q, et al. Early barriers to neonatal porcine islet engraftment in a dual transplant model[J]. Am J Transplant, 2018, 18(4):998-1006. DOI: 10.1111/ajt.14601.
[52]	CHENG Y, WANG B, LI H, et al. Mechanism for the instant blood-mediated inflammatory reaction in rat islet transplantation[J]. Transplant Proc, 2017, 49(6):1440-1443. DOI: 10.1016/j.transproceed.2017.03.090.
[53]	KLOSTER-JENSEN K, SAHRAOUI A, VETHE NT, et al. Treatment with tacrolimus and sirolimus reveals no additional adverse effects on human islets in vitro compared to each drug alone but they are reduced by adding glucocorticoids[J]. J Diabetes Res, 2016:4196460. DOI: 10.1155/2016/4196460.
[54]	谭建明, 杨顺良, 蔡锦全, 等.成人胰岛细胞移植25例次临床研究[J/CD].中华细胞与干细胞杂志(电子版), 2011, 1(2):37-41. DOI: 10.3877/cma.j.issn.2095-1221.2011.02.008. TAN JM, YANG SL, CAI JQ, et al. Single center experience of 25 adult islets transplantation[J/CD]. Chin J Cell Stem Cell, 2011, 1(2):37-41. DOI: 10.3877/cma.j.issn.2095-1221.2011.02.008.
[55]	ARIFIN DR, VALDEIG S, ANDERS RA, et al. Magnetoencapsulated human islets xenotransplanted into swine: a comparison of different transplantation sites[J]. Xenotransplantation, 2016, 23(3):211-221. DOI: 10.1111/xen.12235.
[56]	SCHMIDT C. Pancreatic islets find a new transplant home in the omentum[J]. Nat Biotechnol, 2017, 35(1):8. DOI: 10.1038/nbt0117-8.
[57]	GOTO M, JOHANSSON H, MAEDA A, et al. Low molecular weight dextran sulfate prevents the instant blood-mediated inflammatory reaction induced by adult porcine islets[J]. Transplantation, 2004, 77(5):741-747. doi: 10.1097/01.TP.0000114872.26990.4F
[58]	LAU J, JANSSON L, CARLSSON PO. Islets transplanted intraportally into the liver are stimulated to insulin and glucagon release exclusively through the hepatic artery[J]. Am J Transplant, 2006, 6(5 Pt 1):967-975. http://cn.bing.com/academic/profile?id=c49fbe5311f2ca6b7ebd86a2078bcfce&encoded=0&v=paper_preview&mkt=zh-cn