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间质干细胞与未成熟树突状细胞共移植增强胰岛同种异体移植物的血糖控制。

Cotransplantation of Mesenchymal Stem Cells and Immature Dendritic Cells Potentiates the Blood Glucose Control of Islet Allografts.

机构信息

Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, China.

Center Laboratory, Peking University Shenzhen Hospital, Shenzhen, China.

出版信息

Biomed Res Int. 2017;2017:4107943. doi: 10.1155/2017/4107943. Epub 2017 Dec 19.

DOI:10.1155/2017/4107943
PMID:29410963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5749219/
Abstract

BACKGROUND

Transplantation of islets is a promising alternative to treat type 1 diabetes (T1D), but graft rejection is the major obstacle to its application in clinical practice. We evaluated the effects of mesenchymal stem cells (MSCs) and immature dendritic cells (imDCs) on islet transplantation in diabetic model.

METHODS

The streptozotocin T1D model was established in BABL/c mice. Rat islets were isolated and identified with dithizone (DTZ) staining. MSCs and imDCs were isolated from bone marrow of syngenic mice. Islets, alone or along with MSCs and/or imDCs, were transplanted to the left kidney capsule of diabetic mice. The blood glucose levels and glycosylated hemoglobin levels after transplantation were monitored.

RESULTS

Cotransplantation significantly decreased blood glucose and glycosylated hemoglobin levels in the diabetes mice. Transplantation of 200 islets + 2 × 10 MSCs + 2 × 10 imDCs could not only restore normal blood glucose levels, but also significantly prolong graft survival for 12.6 ± 3.48 days.

CONCLUSIONS

Cotransplantation of allogenic islets with imDCs and/or MSCs can significantly promote graft survival, reverse hyperglycemia, and effectively control the glycosylated hemoglobin levels.

摘要

背景

胰岛移植是治疗 1 型糖尿病(T1D)的一种很有前途的方法,但移植物排斥仍是其在临床应用中的主要障碍。我们评估了间充质干细胞(MSCs)和未成熟树突状细胞(imDCs)对胰岛移植治疗糖尿病模型的影响。

方法

链脲佐菌素诱导 BABL/c 小鼠 T1D 模型,用二硫代丁二酸钠(DTZ)染色鉴定分离的胰岛。从同基因小鼠的骨髓中分离 MSC 和 imDC。将胰岛,单独或与 MSCs 和/或 imDC 一起,移植到糖尿病小鼠的左肾包膜中。监测移植后的血糖和糖化血红蛋白水平。

结果

共移植可显著降低糖尿病小鼠的血糖和糖化血红蛋白水平。移植 200 个胰岛+2×10 MSC+2×10 imDC 不仅可以恢复正常的血糖水平,还可以显著延长移植物存活时间至 12.6±3.48 天。

结论

同种异体胰岛与 imDC 和/或 MSC 共移植可以显著促进移植物存活,逆转高血糖,并有效控制糖化血红蛋白水平。

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Cotransplantation of Mesenchymal Stem Cells and Immature Dendritic Cells Potentiates the Blood Glucose Control of Islet Allografts.间质干细胞与未成熟树突状细胞共移植增强胰岛同种异体移植物的血糖控制。
Biomed Res Int. 2017;2017:4107943. doi: 10.1155/2017/4107943. Epub 2017 Dec 19.
2
Co-transplantation of islets with mesenchymal stem cells in microcapsules demonstrates graft outcome can be improved in an isolated-graft model of islet transplantation in mice.微囊共移植胰岛与间充质干细胞可改善胰岛移植在小鼠分离移植模型中的移植物结局。
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Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo.脂肪组织来源的间充质基质细胞在体外和体内胰岛微环境中均能有效地分化为胰岛素分泌细胞。
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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。
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Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.间质干细胞和胰岛细胞电融合用于糖尿病治疗:大鼠模型。
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Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats.骨髓间充质干细胞改善糖尿病大鼠胰岛移植功能。
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Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model.间充质基质细胞改善同种异体移植小鼠模型中胰岛的存活和功能。
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本文引用的文献

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An improved protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow.一种从小鼠骨髓中分离和培养间充质干细胞的改良方案。
J Orthop Translat. 2014 Aug 27;3(1):26-33. doi: 10.1016/j.jot.2014.07.005. eCollection 2015 Jan.
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Clinical pancreatic islet transplantation.临床胰腺胰岛移植。
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Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia.1型糖尿病合并严重低血糖患者人胰岛移植3期试验
免疫保护配方和工艺策略可提高移植胰岛的存活率和功能。
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Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement.干细胞移植治疗 1 型糖尿病:从胰岛素替代到β细胞替代。
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Organizational update: the world health organization global status report on noncommunicable diseases 2014; one more landmark step in the combat against stroke and vascular disease.组织动态:《2014年世界卫生组织非传染性疾病全球状况报告》;抗击中风和血管疾病的又一里程碑式进展。
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Tolerance induction and reversal of diabetes in mice transplanted with human embryonic stem cell-derived pancreatic endoderm.人胚胎干细胞源性胰腺内胚层移植诱导小鼠免疫耐受及逆转糖尿病
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Tolerogenic dendritic cells and their applications in transplantation.耐受性树突状细胞及其在移植中的应用。
Cell Mol Immunol. 2015 Jan;12(1):24-30. doi: 10.1038/cmi.2014.52. Epub 2014 Aug 11.
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Type 1 diabetes through the life span: a position statement of the American Diabetes Association.1型糖尿病的全生命周期:美国糖尿病协会的立场声明
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Bone marrow mesenchymal stem cells promote the repair of islets from diabetic mice through paracrine actions.骨髓间充质干细胞通过旁分泌作用促进糖尿病小鼠胰岛的修复。
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Alternative immunomodulatory strategies for xenotransplantation: CD80/CD86-CTLA4 pathway-modified immature dendritic cells promote xenograft survival.异种移植的免疫调节策略选择:CD80/CD86-CTLA4 通路修饰的未成熟树突状细胞促进异种移植物的存活。
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