分化型与未分化型脐带华通氏胶间充质干细胞对链脲佐菌素诱导的糖尿病大鼠治疗效果的比较
Comparison between the therapeutic effects of differentiated and undifferentiated Wharton's jelly mesenchymal stem cells in rats with streptozotocin-induced diabetes.
作者信息
Hsiao Chen-Yuan, Chen Tien-Hua, Huang Ben-Shian, Chen Po-Han, Su Cheng-Hsi, Shyu Jia-Fwu, Tsai Pei-Jiun
机构信息
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei 112, Taiwan.
出版信息
World J Stem Cells. 2020 Feb 26;12(2):139-151. doi: 10.4252/wjsc.v12.i2.139.
BACKGROUND
Despite the availability of current therapies, including oral antidiabetic drugs and insulin, for controlling the symptoms caused by high blood glucose, it is difficult to cure diabetes mellitus, especially type 1 diabetes mellitus.
AIM
Cell therapies using mesenchymal stem cells (MSCs) may be a promising option. However, the therapeutic mechanisms by which MSCs exert their effects, such as whether they can differentiate into insulin-producing cells (IPCs) before transplantation, are uncertain.
METHODS
In this study, we used three types of differentiation media over 10 d to generate IPCs from human Wharton's jelly MSCs (hWJ-MSCs). We further transplanted the undifferentiated hWJ-MSCs and differentiated IPCs derived from them into the portal vein of rats with streptozotocin-induced diabetes, and recorded the physiological and pathological changes.
RESULTS
Using fluorescent staining and C-peptide enzyme-linked immunoassay, we were able to successfully induce the differentiation of hWJ-MSCs into IPCs. Transplantation of both IPCs derived from hWJ-MSCs and undifferentiated hWJ-MSCs had the therapeutic effect of ameliorating blood glucose levels and improving intraperitoneal glucose tolerance tests. The transplanted IPCs homed to the pancreas and functionally survived for at least 8 wk after transplantation, whereas the undifferentiated hWJ-MSCs were able to improve the insulitis and ameliorate the serum inflammatory cytokine in streptozotocin-induced diabetic rats.
CONCLUSION
Differentiated IPCs can significantly improve blood glucose levels in diabetic rats due to the continuous secretion of insulin by transplanted cells that survive in the islets of diabetic rats. Transplantation of undifferentiated hWJ-MSCs can significantly improve insulitis and re-balance the inflammatory condition in diabetic rats with only a slight improvement in blood glucose levels.
背景
尽管目前有包括口服抗糖尿病药物和胰岛素在内的疗法可用于控制高血糖引起的症状，但糖尿病，尤其是1型糖尿病，仍难以治愈。
目的
使用间充质干细胞（MSC）的细胞疗法可能是一种有前景的选择。然而，MSC发挥作用的治疗机制，比如它们在移植前是否能分化为胰岛素产生细胞（IPC），尚不确定。
方法
在本研究中，我们使用三种分化培养基，在10天内从人脐带华通氏胶间充质干细胞（hWJ-MSC）生成IPC。我们进一步将未分化的hWJ-MSC及其分化得到的IPC移植到链脲佐菌素诱导的糖尿病大鼠的门静脉中，并记录生理和病理变化。
结果
通过荧光染色和C肽酶联免疫测定，我们成功诱导hWJ-MSC分化为IPC。移植hWJ-MSC来源的IPC和未分化的hWJ-MSC均具有改善血糖水平和提高腹腔葡萄糖耐量试验的治疗效果。移植的IPC归巢到胰腺，移植后至少在功能上存活了8周，而未分化的hWJ-MSC能够改善链脲佐菌素诱导的糖尿病大鼠的胰岛炎并减轻血清炎症细胞因子。
结论
分化的IPC能显著改善糖尿病大鼠的血糖水平，这是因为移植到糖尿病大鼠胰岛中存活的细胞持续分泌胰岛素。未分化的hWJ-MSC移植能显著改善胰岛炎，并使糖尿病大鼠的炎症状态重新平衡，血糖水平仅略有改善。
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