The progress of islet cells co-transplantation with bone marrow mesenchymal stem cells inthe treatment of diabetes_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SHI Jing ^1,2 , YAO Yutong ¹ , FENG Tianhang ³ , WEI Lingling ¹ , LAI Chunyou ¹ , DENG Shaoping ¹ ,  HUANG Xiaolun ¹

1. Cell Transplantation Center, Affiliated Hospital of University of Electronic Science and Technology of China, Sichuan Provincial People’s Hospital, Chengdu 610072, P. R. China;
2. Molecular Medicine Laboratory, Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region, Chengdu 610041, P. R. China;
3. Zunyi Medical University, Zunyi, Guizhou 563003, P. R. China;

Corresponding author：

HUANG Xiaolun, Email: huangxiaolun@med.uestc.edu.cn

Keywords：

diabetes; islet cells transplantation; bone marrow mesenchymal stem cell; review

DOI：

10.7507/1007-9424.201711040

Video：

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Objective To summarize the feasibility and safety of the islet cells co-transplantation with bone marrow mesenchymal stem cells (BMSCs) in the treatment of diabetes. Methods The latest progress and new achievements of islet cells transplantation and BMSCs transplantation in treatment of diabetes in the world were analyzed and reviewed. Results At present, the pancreas transplantation and the islet cells transplantation were mainly treatments for diabetes, the pancreas transplantation had disadvantages of large trauma and high mortality; the islet cells transplantation was safe, but had disadvantages of strong rejection, and the survival time of islets cells were short which affected the treatment effect of diabetes. The BMSCs co-transplanted with the islet cells could prolong the survival time of islet cells and could alleviate the rejection in body, so the co-transplantation can be more effective in treatment of diabetes. Conclusion The BMSCs co-transplant with the islet cells could reduce the rejection in vivo, reduce the inflammation in vivo, prolong the survival time of islet cells, extend the time of normal glucose, which may become the new treatment method for the diabetes.

Citation： SHI Jing, YAO Yutong, FENG Tianhang, WEI Lingling, LAI Chunyou, DENG Shaoping, HUANG Xiaolun. The progress of islet cells co-transplantation with bone marrow mesenchymal stem cells inthe treatment of diabetes. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(5): 635-638. doi: 10.7507/1007-9424.201711040 Copy

1.	Liu X, Li X, Zhang N, et al. Bioengineering strategies for the treatment of type Ⅰ diabetes. J Biomed Nanotechnol, 2016, 12(4): 581-601.
2.	Gonder-Frederick LA, Shepard JA, Grabman JH, et al. Psychology, technology, and diabetes management. Am Psychol, 2016, 71(7): 577-589.
3.	Park CG, Bottino R, Hawthorne WJ. Current status of islet xenotransplantation. Int J Surg, 2015, 23(Pt B): 261-266.
4.	Ahearn AJ, Parekh JR, Posselt AM. Islet transplantation for type 1 diabetes: where are we now? Expert Rev Clin Immunol, 2015, 11(1): 59-68.
5.	Orozakunov E, Akyol C, Cakmak A, et al. Pancreas transplantation: experience of single center. Chirurgia (Bucur), 2014, 109(3): 310-312.
6.	姚豫桐, 魏玲玲, 杨卯竹, 等. 同种异体胰岛移植治疗 1 型糖尿病 10 例及随访观察 3 年的临床研究. 中华器官移植杂志, 2016, 37(2): 90-94.
7.	邓绍平, 朱一帆, 魏玲玲, 等. 胰岛移植治疗糖尿病的新进展. 实用医院临床杂志, 2011, 8(6): 1-5.
8.	Deters NA, Stokes RA, Gunton JE. Islet transplantation: factors in short-term islet survival. Arch Immunol Ther Exp (Warsz), 2011, 59(6): 421-429.
9.	Vanikar AV, Trivedi HL, Thakkar UG. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus. Cytotherapy, 2016, 18(9): 1077-1086.
10.	Tang X, Chen F, Lin Q, et al. Bone marrow mesenchymal stem cells repair the hippocampal neurons and increase the expression of IGF-1 after cardiac arrest in rats. Exp Ther Med, 2017, 14(5): 4312-4320.
11.	Ma C, Wei Q, Cao B, et al. A multifunctional bioactive material that stimulates osteogenesis and promotes the vascularization bone marrow stem cells and their resistance to bacterial infection. PLoS One, 2017, 12(3): e0172499.
12.	Kiernan CH, Hoogduijn MJ, Franquesa M, et al. Allogeneic chondrogenically differentiated human mesenchymal stromal cells do not induce immunogenic responses from T lymphocytes in vitro. Cytotherapy, 2016, 18(8): 957-969.
13.	Min H, Ding J, Wen Y, et al. Combinatorial treatment of bone marrow transplantation and regulatory T cells improves glycemia in Streptozotocin-diabetic mice. Exp Clin Endocrinol Diabetes, 2015, 123(10): 638-644.
14.	Wu X, Wang Y, Xu J, et al. MM-BMSCs induce naïve CD4⁺ T lymphocytes dysfunction through fibroblast activation protein α. Oncotarget, 2017, 8(32): 52614-52628.
15.	Watanabe S, Uchida K, Nakajima H, et al. Early transplantation of mesenchymal stem cells after spinal cord injury relieves pain hypersensitivity through suppression of pain-related signaling cascades and reduced inflammatory cell recruitment. Stem Cells, 2015, 33(6): 1902-1914.
16.	Pieróg J, Tamo L, Fakin R, et al. Bone marrow stem cells modified with human interleukin 10 attenuate acute rejection in rat lung allotransplantation. Eur J Cardiothorac Surg, 2018, 53(1): 194-200.
17.	Xu LJ, Wang SF, Wang DQ, et al. Adipose-derived stromal cells resemble bone marrow stromal cells in hepatocyte differentiation potential in vitro and in vivo. World J Gastroenterol, 2017, 23(38): 6973-6982.
18.	Cai S, Tsui YP, Tam KW, et al. Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells. Stem Cell Reports, 2017, 9(4): 1097-1108.
19.	Jacobson EF, Tzanakakis ES. Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions. J Biol Eng, 2017, 11: 21.
20.	Jeong YM, Cheng XW, Lee S, et al. Preconditioning with far-infrared irradiation enhances proliferation, cell survival, and migration of rat bone marrow-derived stem cells via CXCR4-ERK pathways. Sci Rep, 2017, 7(1): 13718.
21.	Scuteri A, Donzelli E, Rodriguez-Menendez V, et al. A double mechanism for the mesenchymal stem cells’ positive effect on pancreatic islets. PLoS One, 2014, 9(1): e84309.
22.	Vaithilingam V, Evans MDM, Lewy DM, et al. Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted. Sci Rep, 2017, 7(1): 10059.
23.	Miladpour B, Rasti M, Owji AA, et al. Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro. J Endocrinol Invest, 2017, 40(5): 513-521.
24.	Borg DJ, Weigelt M, Wilhelm C, et al. Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. Diabetologia, 2014, 57(3): 522-531.
25.	Aali E, Mirzamohammadi S, Ghaznavi H, et al. A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats. J Diabetes Metab Disord, 2014, 13(1): 76.
26.	李伟娟, 田烁, 刘阁玲, 等. 移植共培养的骨髓间充质干细胞与胰岛细胞对糖尿病大鼠的降血糖作用. 吉林大学学报 (医学版), 2010, 36(6): 1079-1083.
27.	Yanai G, Hayashi T, Zhi Q, et al. Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model. PLoS One, 2013, 8(5): e64499.
28.	Gaglia JL, Shapiro AM, Weir GC. Islet transplantation: progress and challenge. Arch Med Res, 2005, 36(3): 273-280.
29.	Balamurugan AN, Bottino R, Giannoukakis N, et al. Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes. Pancreas, 2006, 32(3): 231-243.
30.	Unsal IO, Ginis Z, Pinarli FA, et al. Comparison of therapeutic characteristics of islet cell transplantation simultaneous with pancreatic mesenchymal stem cell transplantation in rats with type 1 diabetes mellitus. Stem Cell Rev, 2015, 11(3): 526-532.
31.	Oh BJ, Oh SH, Jin SM, et al. Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts. Am J Transplant, 2013, 13(6): 1429-1440.
32.	Cunha JP, Gysemans C, Gillard P, et al. Stem-cell-based therapies for improving islet transplantation outcomes in type 1 diabetes. Curr Diabetes Rev, 2018, 14(1): 3-13.
33.	Pan XH, Song QQ, Dai JJ, et al. Transplantation of bone marrow mesenchymal stem cells for the treatment of type 2 diabetes in a macaque model. Cells Tissues Organs, 2013, 198(6): 414-427.
34.	El-Badri N, Ghoneim MA. Mesenchymal stem cell therapy in diabetes mellitus: progress and challenges. J Nucleic Acids, 2013, 2013: 194858.
35.	Wu T, Levay-Young B, Heuss N, et al. Inducing tolerance to MHC-matched allogeneic islet grafts in diabetic NOD mice by simultaneous islet and bone marrow transplantation under nonirradiative and nonmyeloablative conditioning therapy. Transplantation, 2002, 74(1): 22-27.
36.	Ikebukuro K, Adachi Y, Yamada Y, et al. Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats. Transplantation, 2002, 73(4): 512-518.
37.	Jacamo R, Davis RE, Ling X, et al. Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia. Oncotarget, 2017, 8(48): 83354-83369.
38.	Ben Nasr M, Vergani A, Avruch J, et al. Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site. Acta Diabetol, 2015, 52(5): 917-927.
39.	罗芳, 吴志贤, 陶小琴, 等. 1 例肾-胰岛细胞和干细胞移植治疗Ⅰ型糖尿病合并尿毒症护理体会. 福州总医院学报, 2009, 2(2): 137-138.
40.	Grapensparr L, Vasylovska S, Li Z, et al. Co-transplantation of human pancreatic islets with post-migratory neural crest stem cells increases β-cell proliferation and vascular and neural regrowth. J Clin Endocrinol Metab, 2015, 100(4): E583-E590.
41.	Monfrini M, Donzelli E, Rodriguez-Menendez V, et al. Therapeutic potential of mesenchymal stem cells for the treatment of diabetic peripheral neuropathy. Exp Neurol, 2017, 288: 75-84.

1. Liu X, Li X, Zhang N, et al. Bioengineering strategies for the treatment of type Ⅰ diabetes. J Biomed Nanotechnol, 2016, 12(4): 581-601.
2. Gonder-Frederick LA, Shepard JA, Grabman JH, et al. Psychology, technology, and diabetes management. Am Psychol, 2016, 71(7): 577-589.
3. Park CG, Bottino R, Hawthorne WJ. Current status of islet xenotransplantation. Int J Surg, 2015, 23(Pt B): 261-266.
4. Ahearn AJ, Parekh JR, Posselt AM. Islet transplantation for type 1 diabetes: where are we now? Expert Rev Clin Immunol, 2015, 11(1): 59-68.
5. Orozakunov E, Akyol C, Cakmak A, et al. Pancreas transplantation: experience of single center. Chirurgia (Bucur), 2014, 109(3): 310-312.
6. 姚豫桐, 魏玲玲, 杨卯竹, 等. 同种异体胰岛移植治疗 1 型糖尿病 10 例及随访观察 3 年的临床研究. 中华器官移植杂志, 2016, 37(2): 90-94.
7. 邓绍平, 朱一帆, 魏玲玲, 等. 胰岛移植治疗糖尿病的新进展. 实用医院临床杂志, 2011, 8(6): 1-5.
8. Deters NA, Stokes RA, Gunton JE. Islet transplantation: factors in short-term islet survival. Arch Immunol Ther Exp (Warsz), 2011, 59(6): 421-429.
9. Vanikar AV, Trivedi HL, Thakkar UG. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus. Cytotherapy, 2016, 18(9): 1077-1086.
10. Tang X, Chen F, Lin Q, et al. Bone marrow mesenchymal stem cells repair the hippocampal neurons and increase the expression of IGF-1 after cardiac arrest in rats. Exp Ther Med, 2017, 14(5): 4312-4320.
11. Ma C, Wei Q, Cao B, et al. A multifunctional bioactive material that stimulates osteogenesis and promotes the vascularization bone marrow stem cells and their resistance to bacterial infection. PLoS One, 2017, 12(3): e0172499.
12. Kiernan CH, Hoogduijn MJ, Franquesa M, et al. Allogeneic chondrogenically differentiated human mesenchymal stromal cells do not induce immunogenic responses from T lymphocytes in vitro. Cytotherapy, 2016, 18(8): 957-969.
13. Min H, Ding J, Wen Y, et al. Combinatorial treatment of bone marrow transplantation and regulatory T cells improves glycemia in Streptozotocin-diabetic mice. Exp Clin Endocrinol Diabetes, 2015, 123(10): 638-644.
14. Wu X, Wang Y, Xu J, et al. MM-BMSCs induce naïve CD4⁺ T lymphocytes dysfunction through fibroblast activation protein α. Oncotarget, 2017, 8(32): 52614-52628.
15. Watanabe S, Uchida K, Nakajima H, et al. Early transplantation of mesenchymal stem cells after spinal cord injury relieves pain hypersensitivity through suppression of pain-related signaling cascades and reduced inflammatory cell recruitment. Stem Cells, 2015, 33(6): 1902-1914.
16. Pieróg J, Tamo L, Fakin R, et al. Bone marrow stem cells modified with human interleukin 10 attenuate acute rejection in rat lung allotransplantation. Eur J Cardiothorac Surg, 2018, 53(1): 194-200.
17. Xu LJ, Wang SF, Wang DQ, et al. Adipose-derived stromal cells resemble bone marrow stromal cells in hepatocyte differentiation potential in vitro and in vivo. World J Gastroenterol, 2017, 23(38): 6973-6982.
18. Cai S, Tsui YP, Tam KW, et al. Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells. Stem Cell Reports, 2017, 9(4): 1097-1108.
19. Jacobson EF, Tzanakakis ES. Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions. J Biol Eng, 2017, 11: 21.
20. Jeong YM, Cheng XW, Lee S, et al. Preconditioning with far-infrared irradiation enhances proliferation, cell survival, and migration of rat bone marrow-derived stem cells via CXCR4-ERK pathways. Sci Rep, 2017, 7(1): 13718.
21. Scuteri A, Donzelli E, Rodriguez-Menendez V, et al. A double mechanism for the mesenchymal stem cells’ positive effect on pancreatic islets. PLoS One, 2014, 9(1): e84309.
22. Vaithilingam V, Evans MDM, Lewy DM, et al. Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted. Sci Rep, 2017, 7(1): 10059.
23. Miladpour B, Rasti M, Owji AA, et al. Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro. J Endocrinol Invest, 2017, 40(5): 513-521.
24. Borg DJ, Weigelt M, Wilhelm C, et al. Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. Diabetologia, 2014, 57(3): 522-531.
25. Aali E, Mirzamohammadi S, Ghaznavi H, et al. A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats. J Diabetes Metab Disord, 2014, 13(1): 76.
26. 李伟娟, 田烁, 刘阁玲, 等. 移植共培养的骨髓间充质干细胞与胰岛细胞对糖尿病大鼠的降血糖作用. 吉林大学学报 (医学版), 2010, 36(6): 1079-1083.
27. Yanai G, Hayashi T, Zhi Q, et al. Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model. PLoS One, 2013, 8(5): e64499.
28. Gaglia JL, Shapiro AM, Weir GC. Islet transplantation: progress and challenge. Arch Med Res, 2005, 36(3): 273-280.
29. Balamurugan AN, Bottino R, Giannoukakis N, et al. Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes. Pancreas, 2006, 32(3): 231-243.
30. Unsal IO, Ginis Z, Pinarli FA, et al. Comparison of therapeutic characteristics of islet cell transplantation simultaneous with pancreatic mesenchymal stem cell transplantation in rats with type 1 diabetes mellitus. Stem Cell Rev, 2015, 11(3): 526-532.
31. Oh BJ, Oh SH, Jin SM, et al. Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts. Am J Transplant, 2013, 13(6): 1429-1440.
32. Cunha JP, Gysemans C, Gillard P, et al. Stem-cell-based therapies for improving islet transplantation outcomes in type 1 diabetes. Curr Diabetes Rev, 2018, 14(1): 3-13.
33. Pan XH, Song QQ, Dai JJ, et al. Transplantation of bone marrow mesenchymal stem cells for the treatment of type 2 diabetes in a macaque model. Cells Tissues Organs, 2013, 198(6): 414-427.
34. El-Badri N, Ghoneim MA. Mesenchymal stem cell therapy in diabetes mellitus: progress and challenges. J Nucleic Acids, 2013, 2013: 194858.
35. Wu T, Levay-Young B, Heuss N, et al. Inducing tolerance to MHC-matched allogeneic islet grafts in diabetic NOD mice by simultaneous islet and bone marrow transplantation under nonirradiative and nonmyeloablative conditioning therapy. Transplantation, 2002, 74(1): 22-27.
36. Ikebukuro K, Adachi Y, Yamada Y, et al. Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats. Transplantation, 2002, 73(4): 512-518.
37. Jacamo R, Davis RE, Ling X, et al. Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia. Oncotarget, 2017, 8(48): 83354-83369.
38. Ben Nasr M, Vergani A, Avruch J, et al. Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site. Acta Diabetol, 2015, 52(5): 917-927.
39. 罗芳, 吴志贤, 陶小琴, 等. 1 例肾-胰岛细胞和干细胞移植治疗Ⅰ型糖尿病合并尿毒症护理体会. 福州总医院学报, 2009, 2(2): 137-138.
40. Grapensparr L, Vasylovska S, Li Z, et al. Co-transplantation of human pancreatic islets with post-migratory neural crest stem cells increases β-cell proliferation and vascular and neural regrowth. J Clin Endocrinol Metab, 2015, 100(4): E583-E590.
41. Monfrini M, Donzelli E, Rodriguez-Menendez V, et al. Therapeutic potential of mesenchymal stem cells for the treatment of diabetic peripheral neuropathy. Exp Neurol, 2017, 288: 75-84.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The progress of islet cells co-transplantation with bone marrow mesenchymal stem cells inthe treatment of diabetes

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