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间充质干细胞作为胰岛移植的饲养层细胞

Mesenchymal stem cells as feeder cells for pancreatic islet transplants.

作者信息

Sordi Valeria, Piemonti Lorenzo

机构信息

San Raffaele Diabetes Research Institute (HSR-DRI), Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

出版信息

Rev Diabet Stud. 2010 Summer;7(2):132-43. doi: 10.1900/RDS.2010.7.132. Epub 2010 Aug 10.

DOI:10.1900/RDS.2010.7.132
PMID:21060972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2989786/
Abstract

Allogeneic islet transplantation serves as a source of insulin-secreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients.

摘要

同种异体胰岛移植可作为分泌胰岛素的β细胞来源,用于维持正常血糖水平和治疗糖尿病。然而,胰岛供应有限、胰岛移植失败率高以及需要终身进行非特异性免疫抑制治疗是这种治疗方法广泛应用的主要障碍。为克服这些问题,胰腺胰岛移植最近被认为是成体干细胞“治疗可塑性”的一个潜在靶点。事实上,新的研究结果表明,干细胞/前体细胞,尤其是间充质干细胞,与胰岛共同移植可通过旁观者机制促进组织植入和β细胞存活,主要是通过产生细胞保护和免疫调节分子的微环境来实现。这一证据不断挑战干细胞/前体细胞在糖尿病治疗中仅通过β细胞替代发挥作用的有限观点。它提出干细胞还可作为胰岛的“饲养”细胞,以及移植保护、组织血管再生和免疫耐受的支持者。本文综述了将干细胞共同移植作为改善胰岛移植策略的经验。它强调,理解其中涉及的机制将有助于确定新的分子靶点,并促进开发治疗1型和2型糖尿病患者的新药理学策略。

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Mesenchymal stem cells as feeder cells for pancreatic islet transplants.间充质干细胞作为胰岛移植的饲养层细胞
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2
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MSCs feeder layers induce SMG self-organization and branching morphogenesis.间充质干细胞饲养层诱导颌下腺自我组织和分支形态发生。
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Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model.间质干细胞增强大鼠坐骨神经修复和后肢移植模型中的神经再生。
Sci Rep. 2016 Aug 11;6:31306. doi: 10.1038/srep31306.
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β-MSCs: successful fusion of MSCs with β-cells results in a β-cell like phenotype.β-间充质干细胞:间充质干细胞与β细胞成功融合会产生类似β细胞的表型。
Oncotarget. 2016 Aug 2;7(31):48963-48977. doi: 10.18632/oncotarget.10214.
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本文引用的文献

1
Mesenchymal stem cells enhance allogeneic islet engraftment in nonhuman primates.间充质干细胞增强非人类灵长类动物同种异体胰岛移植物的植入。
Diabetes. 2010 Oct;59(10):2558-68. doi: 10.2337/db10-0136. Epub 2010 Jul 9.
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Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function.间质干细胞和胰岛共移植促进移植物再血管化和功能。
Transplantation. 2010 Jun 27;89(12):1438-45. doi: 10.1097/tp.0b013e3181db09c4.
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Angiomyeloproliferative lesions following autologous stem cell therapy.自体干细胞治疗后的血管肌纤维母细胞瘤样病变。
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Mesenchymal stem cells prevent acute rejection and prolong graft function in pancreatic islet transplantation.间充质干细胞可预防胰岛移植的急性排斥反应并延长移植物功能。
Diabetes Technol Ther. 2010 Jun;12(6):435-46. doi: 10.1089/dia.2009.0154.
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Immune modulation of co-transplantation mesenchymal stem cells with islet on T and dendritic cells.胰岛与间质干细胞共移植对 T 和树突状细胞的免疫调节。
Clin Exp Immunol. 2010 Aug;161(2):357-63. doi: 10.1111/j.1365-2249.2010.04178.x. Epub 2010 May 7.
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Co-graft of allogeneic immune regulatory neural stem cells (NPC) and pancreatic islets mediates tolerance, while inducing NPC-derived tumors in mice.同种异体免疫调节神经干细胞(NPC)和胰岛共移植可介导免疫耐受,但会在小鼠中诱导 NPC 衍生肿瘤。
PLoS One. 2010 Apr 27;5(4):e10357. doi: 10.1371/journal.pone.0010357.
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Trophic molecules derived from human mesenchymal stem cells enhance survival, function, and angiogenesis of isolated islets after transplantation.源自人骨髓间充质干细胞的营养分子可增强移植后分离胰岛的存活、功能和血管生成。
Transplantation. 2010 Mar 15;89(5):509-17. doi: 10.1097/TP.0b013e3181c7dc99.
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Bone marrow cell cotransplantation with islets improves their vascularization and function.骨髓细胞与胰岛共移植可改善其血管化和功能。
Transplantation. 2010 Mar 27;89(6):686-93. doi: 10.1097/TP.0b013e3181cb3e8d.
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Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.临床级人基质细胞的生产:非整倍体的发生而无转化。
Blood. 2010 Feb 25;115(8):1549-53. doi: 10.1182/blood-2009-05-219907. Epub 2009 Dec 23.
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Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function.在胰腺组织培养中出现的间充质细胞是骨髓来源的干细胞,具有改善移植胰岛功能的能力。
Stem Cells. 2010 Jan;28(1):140-51. doi: 10.1002/stem.259.