Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Stem Cells and Transgenic Technology Research Center (STTRC), Shahid Chamran University of Ahvaz, Ahvaz, Iran.
J Cell Physiol. 2019 Jul;234(7):10196-10204. doi: 10.1002/jcp.27689. Epub 2018 Nov 1.
Diabetes mellitus is an autoimmune and chronic disorder that is rapidly expanding worldwide due to increasing obesity. In the current study, we were able to design a reliable 3-dimensional differentiation process of human Wharton's jelly mesenchymal stem cells into pancreatic beta cell precursors (PBCPs) and detected that transplanted PBCPs could improve hyperglycemia in a diabetes-induced model in mice. Polylactic acid/chitosan nanofibrous scaffold was prepared using an electrospinning method. Quantitative real-time reverse transcription-polymerase chain reaction and immunocytochemistry analysis were carried out to assess pancreatic marker expression in the differentiated cells. PBCPs were transplanted under the kidney capsule of diabetic mice that induced streptozotocin injection 14 days before the transplantation. Moreover, an intraperitoneal glucose tolerance test (ipGTT) was carried out 2 and 4 weeks after the transplantation to measure the reaction to a sudden increase of the blood glucose level in the transplanted animals. The results indicated that the expression of SRY (sex determining region Y)-box (Sox17), forkhead box A2 (FoxA2), pancreatic and duodenal homeobox 1 (Pdx1), neurogenin 3 (Ngn3), hepatic nuclear factor 4, alpha (Hnf4α), and NK2 homeobox 2 (Nkx2.2) were increased significantly in the differentiated cells compared with that of the control group. In the current study, the diabetic disease was confirmed by measuring blood glucose and proved by conducting some other behavioral tests. After the PBCPs transplantation in a diabetic model, the ipGTT and hyperglycemia investigation during the determinant times confirmed the disease's significant improvement in the experimental models. In this study, some preclinical data suggested that the transplantation of PBCPs associated with appropriate nanofiber scaffold can be utilized for the treatment of diabetes models. In addition, studies are required to elucidate the molecular mechanism of PBCPs acting in diabetes models before being used for patients with diabetes.
糖尿病是一种自身免疫性和慢性疾病，由于肥胖症的增加，在全球范围内迅速蔓延。在本研究中，我们能够设计出一种可靠的三维分化过程，将人沃顿氏胶间充质干细胞分化为胰腺β细胞前体（PBCP），并检测到移植的 PBCP 可以改善糖尿病诱导模型中小鼠的高血糖症。聚乳酸/壳聚糖纳米纤维支架采用静电纺丝法制备。通过定量实时逆转录聚合酶链反应和免疫细胞化学分析来评估分化细胞中胰腺标志物的表达。在移植前 14 天注射链脲佐菌素诱导糖尿病的小鼠肾包膜下移植 PBCP。此外，在移植后 2 和 4 周进行腹腔内葡萄糖耐量试验（ipGTT），以测量移植动物对血糖水平突然升高的反应。结果表明，与对照组相比，分化细胞中 SRY（性别决定区 Y）-盒（Sox17）、叉头框 A2（FoxA2）、胰腺和十二指肠同源盒 1（Pdx1）、神经生成素 3（Ngn3）、肝核因子 4，α（Hnf4α）和 NK2 同源盒 2（Nkx2.2）的表达显著增加。在本研究中，通过测量血糖来确认糖尿病，并通过进行其他一些行为测试来证实。在糖尿病模型中移植 PBCP 后，在确定的时间进行 ipGTT 和高血糖症调查，证实了实验模型中疾病的显著改善。在这项研究中，一些临床前数据表明，与适当的纳米纤维支架一起移植 PBCP 可用于治疗糖尿病模型。此外，在将 PBCP 用于糖尿病患者之前，需要研究阐明其在糖尿病模型中作用的分子机制。
