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间质基质细胞和脐血细胞共移植治疗糖尿病。

Co-transplantation of mesenchymal stromal cells and cord blood cells in treatment of diabetes.

机构信息

Department of Adult Stem Cell, Institute of Reproduction and Stem Cell Engineering, Central South University, Changsha, Hunan, China.

出版信息

Cytotherapy. 2013 Nov;15(11):1374-84. doi: 10.1016/j.jcyt.2013.06.013.

Abstract

BACKGROUND AIMS

Stem cells provide a promising source for treatment of type 1 diabetes, but the treatment strategy and mechanism remain unclear. The aims of this study were to investigate whether co-transplantation of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) and cord blood mononuclear cells (CB-MNCs) could reverse hyperglycemia in type 1 diabetic mice and to determine the appropriate ratio for co-transplantation. The treatment mechanism was also studied.

METHODS

A simple and efficient isolation method was developed to generate qualified UC-MSCs. UC-MSCs and CB-MNCs were then transplanted into type 1 diabetic mice at different ratios (UC-MSCs to CB-MNCs = 1:1, 1:4, 1:10) to observe the change in blood glucose concentration. Histology, immunohistochemistry, and human Alu polymerase chain reaction assay were performed to evaluate for the presence of donor-derived cells and the repair of endogenous islets. We also induced UC-MSCs into islet-like cells under specific culture conditions to determine their differentiate potential in vitro.

RESULTS

Co-transplantation of UC-MSCs and CB-MNCs at a ratio of 1:4 effectively reversed hyperglycemia in diabetic mice. The detection of human Alu sequence indicated that the engraftment of donor-derived cells had homed into the recipient's pancreas and kidney. Although neither human insulin nor human nuclei antigen was detected in the regenerated pancreas, UC-MSCs could differentiate into insulin-secreted cells in vitro.

CONCLUSIONS

Co-transplantation of UC-MSCs and CB-MNCs at a ratio of 1:4 could efficiently reverse hyperglycemia and repair pancreatic tissue.

摘要

背景目的

干细胞为治疗 1 型糖尿病提供了有前途的来源,但治疗策略和机制仍不清楚。本研究旨在探讨脐带间充质基质细胞(UC-MSCs)和脐血单个核细胞(CB-MNCs)共移植是否能逆转 1 型糖尿病小鼠的高血糖,并确定共移植的合适比例。还研究了治疗机制。

方法

开发了一种简单有效的分离方法来产生合格的 UC-MSCs。然后将 UC-MSCs 和 CB-MNCs 以不同比例(UC-MSCs 与 CB-MNCs=1:1、1:4、1:10)移植到 1 型糖尿病小鼠体内,观察血糖浓度的变化。进行组织学、免疫组织化学和人 Alu 聚合酶链反应检测,以评估供体来源细胞的存在和内源性胰岛的修复情况。我们还在特定的培养条件下将 UC-MSCs 诱导为胰岛样细胞,以确定其体外分化潜能。

结果

UC-MSCs 和 CB-MNCs 以 1:4 的比例共移植可有效逆转糖尿病小鼠的高血糖。人 Alu 序列的检测表明,供体来源细胞的植入已归巢到受者的胰腺和肾脏。尽管在再生胰腺中未检测到人胰岛素或人核抗原,但 UC-MSCs 可在体外分化为胰岛素分泌细胞。

结论

UC-MSCs 和 CB-MNCs 以 1:4 的比例共移植可有效逆转高血糖并修复胰腺组织。

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