Department of Urology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California.
Division of Endocrinology, VA Greater Los Angeles Healthcare System, University of California Los Angeles, Los Angeles, California.
Cytotherapy. 2014 Jan;16(1):41-55. doi: 10.1016/j.jcyt.2013.08.010. Epub 2013 Nov 7.
The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating β-cell injury and restoring β-cell function.
Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation.
AFSC injection resulted in protection from β-cell damage and increased β-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, β-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining β-cell mass and function.
Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous β-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non-genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved.
近年来，已有研究表明羊水干细胞（AFSC）可促进急性和慢性肾损伤及肺衰竭模型中的组织保护和再生。本研究中，我们使用化学诱导的 1 型糖尿病小鼠模型，旨在确定 AFSC 是否可在调节β细胞损伤和恢复β细胞功能方面发挥作用。
链脲佐菌素诱导的糖尿病小鼠接受心脏内注射 AFSC；细胞移植后评估胰岛素通路的形态和生理参数及基因表达谱。
AFSC 注射可防止部分小鼠的β细胞损伤，并促进β细胞再生，表现为血糖和胰岛素水平升高、胰岛质量增加和胰岛结构保持。此外，β细胞的保存/再生与胰岛素受体/PI3K/Akt 信号通路的激活以及血管内皮生长因子-A 的表达相关，后者参与维持β细胞的质量和功能。
我们的研究结果提示，AFSC 在保存和促进内源性β细胞功能和增殖方面具有治疗作用。当在严重高血糖发生之前进行干细胞移植时，AFSC 发挥保护作用，这提示早期干预的重要性。本研究表明，应用源自羊水的非基因工程干细胞群体治疗 1 型糖尿病可能具有益处，并提供了关于实现有益效果的机制的新见解。
