Fumagalli Giulia, Monfrini Marianna, Donzelli Elisabetta, Rodriguez-Menendez Virginia, Bonandrini Barbara, Figliuzzi Marina, Remuzzi Andrea, D'Amico Giovanna, Cavaletti Guido, Scuteri Arianna
Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza (MB), Italy.
PhD Program in Neuroscience, University of Milano-Bicocca, Monza (MB), Italy.
Int J Stem Cells. 2020 Mar 30;13(1):116-126. doi: 10.15283/ijsc19094.
Transplantation of pancreatic islets is an intriguing new therapeutic option to face the worldwide spread problem of Type-I diabetes. Currently, its clinical use is limited by several problems, mainly based on the high number of islets required to restore normoglycaemia and by the low survival of the transplanted tissue. A promising attempt to overcome the limits to such an approach was represented by the use of Mesenchymal Stem Cells (MSC). Despite the encouraging results obtained with murine-derived MSC, little is still known about their protective mechanisms. The aim of the present study was to verify the effectiveness, (besides murine MSC), of clinically relevant human-derived MSC (hMSC) on protecting pancreatic islets, thus also shedding light on the putative differences between MSC of different origin.
Threefold kinds of co-cultures were therefore in vitro set up (direct, indirect and mixed), to analyze the hMSC effect on pancreatic islet survival and function and to study the putative mechanisms involved. Although in a different way with respect to murine MSC, also human derived cells demonstrated to be effective on protecting pancreatic islet survival. This effect could be due to the release of some trophic factors, such as VEGF and Il-6, and by the reduction of inflammatory cytokine TNF-.
Therefore, hMSC confirmed their great clinical potential to improve the feasibility of pancreatic islet transplantation therapy against diabetes.
胰岛移植是应对全球范围内I型糖尿病蔓延问题的一种引人关注的新治疗选择。目前,其临床应用受到若干问题的限制,主要基于恢复正常血糖所需的胰岛数量众多以及移植组织的低存活率。使用间充质干细胞(MSC)是克服这种方法局限性的一种有前景的尝试。尽管从鼠源MSC获得了令人鼓舞的结果,但对其保护机制仍知之甚少。本研究的目的是验证临床相关的人源MSC(hMSC)(除鼠源MSC外)对保护胰岛的有效性,从而也阐明不同来源MSC之间可能存在的差异。
因此,在体外建立了三种共培养方式(直接、间接和混合),以分析hMSC对胰岛存活和功能的影响,并研究其中涉及的可能机制。尽管与鼠源MSC的方式不同,但人源细胞也证明对保护胰岛存活有效。这种作用可能归因于某些营养因子的释放,如血管内皮生长因子(VEGF)和白细胞介素-6(Il-6),以及炎性细胞因子肿瘤坏死因子-α(TNF-α)的减少。
因此,hMSC证实了其在提高胰岛移植治疗糖尿病可行性方面的巨大临床潜力。