Stem Cell Technology Research Center, Tehran, Iran.
Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
J Cell Physiol. 2018 May;233(5):4327-4337. doi: 10.1002/jcp.26266. Epub 2017 Dec 26.
The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels. The viability of induced pancreatic cells was 14 days. The in vitro studies showed that the treatment of hADSCs in the 3D culture resulted in differentiated cells with strong characteristics of IPCs including pancreatic-like cells, the expression of the islet-associated genes at the mRNA and protein levels in comparison of 2D culture group. Furthermore, the immunoassay tests showed that these differentiated cells in these two groups are functional and secreted C-peptide and insulin in a glucose stimulation challenge. The results of our study for the first time demonstrated that the PVA nanofibrous scaffolds along with the optimized differentiation protocol with PRP can enhance the differentiation of IPCs from hADSCs. In conclusion, this study provides a new approach to the future pancreatic tissue engineering and beta cell replacement therapies for T1DM.
已经对源自间充质干细胞的患者特异性人脂肪(hADSCs)进行了研究,例如一系列自体生长因子和纳米纤维支架(3D 培养)可能对 1 型糖尿病(T1DM)患者的再生医学有许多好处。为此,我们建立了聚乙烯醇(PVA)支架和添加富含血小板的血浆(PRP)的分化方案,该方案可将 hADSCs 诱导为胰岛素产生细胞(IPC)。在 3D 培养中,与传统培养(2D)组相比,评估了衍生的 IPC 在 3D 培养中的特性,在 mRNA 和蛋白质水平上进行了评估。诱导的胰腺细胞的活力为 14 天。体外研究表明,3D 培养中 hADSCs 的处理导致具有强 IPC 特征的分化细胞,包括胰岛相关基因在 mRNA 和蛋白质水平上的表达与 2D 培养组相比。此外,免疫测定试验表明,这两组分化细胞具有功能,并且在葡萄糖刺激挑战中分泌 C 肽和胰岛素。我们的研究结果首次表明,PVA 纳米纤维支架以及具有 PRP 的优化分化方案可以增强 hADSCs 中 IPC 的分化。总之,这项研究为未来的胰岛组织工程和 T1DM 的β细胞替代疗法提供了一种新方法。