Amniotic fluid stem cells prevent β-cell injury.

Amniotic fluid stem cells prevent β-cell injury.
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DOI:
10.1016/j.jcyt.2013.08.010
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发表时间:
2014-01
期刊:
影响因子:
4.5
通讯作者:
Perin, Laura
Perin, Laura
中科院分区:
医学3区
文献类型:
--
作者:
Villani, Valentina;Milanesi, Anna;Sedrakyan, Sargis;Da Sacco, Stefano;Angelow, Susanne;Conconi, Maria Teresa;Di Liddo, Rosa;De Filippo, Roger;Perin, Laura

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近年来,羊水干细胞(AFSC)在急性和慢性肾损伤和肺衰竭模型中对组织保护和再生的贡献已被证明。在本研究中,我们使用化学诱导的1型糖尿病小鼠模型来确定AFSC是否可以在调节β细胞损伤和恢复β细胞功能中发挥作用。链脲佐菌素诱导的糖尿病小鼠心内注射AFSC;细胞移植后评估形态学和生理学参数以及胰岛素途径的基因表达谱。AFSC注射导致保护免受β-细胞损伤,并增加小鼠亚组中的β-细胞再生,如葡萄糖和胰岛素水平所示,增加胰岛质量和保留胰岛结构。此外,β细胞保存/再生与胰岛素受体/Pi 3 K/Akt信号通路的激活和参与维持β细胞质量和功能的血管内皮生长因子-A表达相关。我们的研究结果表明AFSC在保护和促进内源性β细胞功能和增殖方面具有治疗作用。AFSC的保护作用是显而易见的,当干细胞移植严重高血糖发生之前,这表明早期干预的重要性。本研究证明了应用来自羊水的非基因工程干细胞群体治疗1型糖尿病的可能益处,并对实现有益效果的机制提供了新的见解。
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.
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