Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa.
Department of Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa.
Adv Exp Med Biol. 2021;1286:163-181. doi: 10.1007/978-3-030-55035-6_12.
Mesenchymal stem cell (MSC) dysfunction is a serious complication in ageing and age-related inflammatory diseases such as type 2 diabetes mellitus. Inflammation and oxidative stress-induced cellular senescence alter the immunomodulatory ability of MSCs and hamper their pro-regenerative function, which in turn leads to an increase in disease severity, maladaptive tissue damage and the development of comorbidities. Targeting stem/progenitor cells to restore their function and/or protect them against impairment could thus improve healing outcomes and significantly enhance the quality of life for diabetic patients. This review discusses the dysregulation of MSCs' immunomodulatory capacity in the context of diabetes mellitus and focuses on intervention strategies aimed at MSC rejuvenation. Research pertaining to the potential therapeutic use of either pharmacological agents (NFкB antagonists), natural products (phytomedicine) or biological agents (exosomes, probiotics) to improve MSC function is discussed and an overview of the most pertinent methodological considerations given. Based on in vitro studies, numerous anti-inflammatory agents, antioxidants and biological agents show tremendous potential to revitalise MSCs. An integrated systems approach and a thorough understanding of complete disease pathology are however required to identify feasible candidates for in vivo targeting of MSCs.
间充质干细胞（MSC）功能障碍是衰老和 2 型糖尿病等与年龄相关的炎症性疾病的严重并发症。炎症和氧化应激诱导的细胞衰老改变了 MSC 的免疫调节能力，并阻碍了其促再生功能，这反过来又导致疾病严重程度增加、适应性组织损伤和合并症的发展。因此，针对干细胞/祖细胞以恢复其功能和/或防止其受损，可能会改善愈合效果并显著提高糖尿病患者的生活质量。这篇综述讨论了糖尿病背景下 MSC 免疫调节能力的失调，并重点介绍了旨在恢复 MSC 活力的干预策略。讨论了潜在治疗用途的研究，包括药理学制剂（NFкB 拮抗剂）、天然产物（植物药）或生物制剂（外泌体、益生菌）改善 MSC 功能，概述了最相关的方法学考虑因素。基于体外研究，许多抗炎、抗氧化和生物制剂具有极大的潜力来恢复 MSC 的活力。然而，需要综合系统的方法和对完整疾病病理学的透彻理解，以确定针对 MSC 进行体内靶向的可行候选物。
