骨髓间充质干细胞移植的糖尿病大鼠干细胞分化评估
Evaluation of stem cell differentiation in diabetic rats transplanted with bone marrow mesenchymal stem cells.
作者信息
Lin P, Chen L, Yang N, Sun Y, Xu Y X
机构信息
Department of Endocrinology, Qilu Hospital, Shandong University, Shandong, China.
出版信息
Transplant Proc. 2009 Jun;41(5):1891-3. doi: 10.1016/j.transproceed.2009.02.078.
OBJECTIVE
Bone marrow mesenchymal stem cell (BM-MSC) transplantation has generated a great deal of excitement as a promising therapeutic strategy for diabetes mellitus. However, the exact mechanisms of reversing hyperglycemia remain elusive. Our objective was to investigate whether stem cell differentiation determined therapeutic efficacy.
MATERIALS AND METHODS
Wistar rats were rendered diabetic by an intraperitoneal injection of streptozotocin. BM-MSCs isolated from diabetic Wistar rats were analyzed for phenotype characteristics. Subsequently, BM-MSCs were transplanted into diabetic rats, followed by intravenous injection of recombinant lentiviruses encoding 2 different small hairpin RNAs (shRNAs) for specific interference with neurogenin 3 (Ngn3). We measured blood glucose levels and insulin and performed histological analysis of the pancreas.
RESULTS
BM-MSCs lowered blood glucose by increasing beta-cell mass compared with sham-operated controls, but this effect was inhibited by interference with the Ngn3 gene.
CONCLUSION
Differentiation of stem cells, including BM-MSCs and endogenous pancreatic stem cells, plays a major role in the process of reversing hyperglycemia.
目的
骨髓间充质干细胞（BM-MSC）移植作为一种有前景的糖尿病治疗策略，已引起广泛关注。然而，逆转高血糖的确切机制仍不清楚。我们的目的是研究干细胞分化是否决定治疗效果。
材料与方法
通过腹腔注射链脲佐菌素使Wistar大鼠患糖尿病。分析从糖尿病Wistar大鼠分离的BM-MSCs的表型特征。随后，将BM-MSCs移植到糖尿病大鼠体内，然后静脉注射编码2种不同小发夹RNA（shRNAs）的重组慢病毒，以特异性干扰神经生成素3（Ngn3）。我们测量了血糖水平和胰岛素，并对胰腺进行了组织学分析。
结果
与假手术对照组相比，BM-MSCs通过增加β细胞数量降低了血糖，但这种作用受到Ngn3基因干扰的抑制。
结论
包括BM-MSCs和内源性胰腺干细胞在内的干细胞分化在逆转高血糖过程中起主要作用。
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