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Protecting islet functional viability using mesenchymal stromal cells
STEM CELLS Translational Medicine ( IF 6 ) Pub Date : 2021-02-05 , DOI: 10.1002/sctm.20-0466
Ella L Hubber 1 , Chloe L Rackham 2 , Peter M Jones 1
Affiliation  

Islet transplantation is an emerging treatment for type 1 diabetes which offers the prospect of physiological control of blood glucose and reductions in acute hypoglycaemic episodes. However, current protocols are limited by a rapid decline in islet functional viability during the isolation process, culture period, and post‐transplantation. Much of this can be attributed to the deleterious effects of hypoxic and cytokine stressors on β cells. One experimental strategy to improve the functional viability of islets is coculture or cotransplantation with mesenchymal stromal cells (MSCs). Numerous studies have shown that MSCs have the capacity to improve islet survival and insulin secretory function, and the mechanisms of these effects are becoming increasingly well understood. In this review, we will focus on recent studies demonstrating the capacity for MSCs to protect islets from hypoxia‐ and cytokine‐induced stress. Islets exposed to acute hypoxia (1%‐2% O2) or to inflammatory cytokines (including IFN‐γ, TNF‐α, and IL‐B) in vitro undergo apoptosis and a rapid decline in glucose‐stimulated insulin secretion. Coculture of islets with MSCs, or with MSC‐conditioned medium, protects from these deleterious effects, primarily with secreted factors. These protective effects are distinct from the immunomodulatory and structural support MSCs provide when cotransplanted with islets. Recent studies suggest that MSCs may support secretory function by the physical transfer of functional mitochondria, particularly to metabolically compromised β cells. Understanding how MSCs respond to stressed islets will facilitate the development of MSC secretome based, cell‐free approaches to supporting islet graft function during transplantation by protecting or repairing β cells.

中文翻译:

使用间充质基质细胞保护胰岛功能活力

胰岛移植是一种新兴的 1 型糖尿病治疗方法,它提供了血糖的生理控制和减少急性低血糖发作的前景。然而,目前的方案受到隔离过程、培养期和移植后胰岛功能活力的快速下降的限制。这在很大程度上可以归因于缺氧和细胞因子应激源对 β 细胞的有害影响。提高胰岛功能活力的一种实验策略是与间充质基质细胞 (MSCs) 共培养或共移植。大量研究表明,间充质干细胞具有改善胰岛存活和胰岛素分泌功能的能力,并且这些作用的机制正变得越来越清楚。在本次审查中,我们将重点关注最近的研究,这些研究证明了 MSCs 保护胰岛免受缺氧和细胞因子诱导的应激的能力。胰岛暴露于急性缺氧(1%-2% O2)或体外炎症细胞因子(包括IFN-γ、TNF-α和IL-B)经历细胞凋亡和葡萄糖刺激的胰岛素分泌迅速下降。胰岛与 MSC 或 MSC 条件培养基的共培养可防止这些有害影响,主要是分泌因子。这些保护作用不同于间充质干细胞与胰岛共同移植时提供的免疫调节和结构支持。最近的研究表明,MSCs 可能通过功能性线粒体的物理转移来支持分泌功能,特别是代谢受损的 β 细胞。了解 MSCs 如何对应激胰岛作出反应将有助于开发基于 MSC 分泌组的无细胞方法,通过保护或修复 β 细胞来支持移植期间的胰岛移植功能。
更新日期:2021-04-15
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