Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC-based generation of functional insulin-producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow-derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy- and GDM-CMSCs/AMSCs to long-term high-glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM-CMSCs/AMSCs, of senescence/stress markers. Short-term high-glucose culture promoted pancreatic transcription factor expression when coupled to a 16-day step-wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon-like peptide-1 and other chemical components, generated functional IPCs from both Healthy- and GDM-CMSCs. Healthy-/GDM-AMSCs displayed betacellulin-sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM-CMSCs possess comparable therapeutic potential with Healthy-CMSCs and can be effectively reprogrammed into insulin-secreting cells.

中文翻译：

---

来自妊娠糖尿病妇女的绒毛膜和羊膜胎盘膜干细胞具有独特的胰岛素分泌细胞分化能力。

患有妊娠糖尿病（GDM）的妇女及其后代有罹患2型糖尿病的高风险。源自胎盘膜的绒毛膜（CMSC）和羊膜间充质干细胞（AMSC）为潜在的糖尿病治疗提供了自体干细胞来源。我们建立了一种基于CMSC / AMSC的功能性胰岛素产生细胞（IPC）生成的方法。与骨髓来源的MSC相比，CMSC / AMSC显着提高了NANOG和OCT4的水平，表明其潜在的广泛分化能力。将健康和GDM-CMSC / AMSC暴露于长期的高糖培养物中会导致活力显着下降，并伴随着衰老/应激标志物的升高（在GDM-CMSC / AMSC中明显如此）。当与16天的逐步分化方案耦合时，短期高糖培养可促进胰腺转录因子的表达。激活素A，视黄酸，表皮生长因子，胰高血糖素样肽1和其他化学成分可从健康和GDM-CMSC生成功能性IPC。健康// GDM-AMSCs表现出β-纤维素蛋白敏感的胰岛素表达，在葡萄糖激发后不会分泌。伴有GDM的病理生理状态可能导致内源性AMSC发生不可逆转的损伤。然而，GDM-CMSC具有与Healthy-CMSC相当的治疗潜力，并且可以有效地重编程为分泌胰岛素的细胞。从健康和GDM-CMSC生成功能IPC。健康// GDM-AMSCs表现出β-纤维素蛋白敏感的胰岛素表达，在葡萄糖激发后不会分泌。伴有GDM的病理生理状态可能导致内源性AMSC发生不可逆转的损伤。然而，GDM-CMSC具有与Healthy-CMSC相当的治疗潜力，并且可以有效地重编程为分泌胰岛素的细胞。从健康和GDM-CMSC生成功能IPC。健康// GDM-AMSCs表现出β-纤维素蛋白敏感的胰岛素表达，在葡萄糖激发后不会分泌。伴有GDM的病理生理状态可能导致内源性AMSC发生不可逆转的损伤。然而，GDM-CMSC具有与Healthy-CMSC相当的治疗潜力，并且可以有效地重编程为分泌胰岛素的细胞。