Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, 411007 Maharashtra, India.
National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, 411007 Maharashtra, India.
Sci Adv. 2022 Jun 24;8(25):eabm6504. doi: 10.1126/sciadv.abm6504.
Aging has been reported to deteriorate the quantity and quality of mesenchymal stem cells (MSCs), which affect their therapeutic use in regenerative medicine. A dearth of age-related stem cell research further restricts their clinical applications. The present study explores the possibility of using MSCs derived from human gingival tissues (GMSCs) for studying their ex vivo growth characteristics and differentiation potential with respect to donor age. GMSCs displayed decreased in vitro adipogenesis and in vitro and in vivo osteogenesis with age, but in vitro neurogenesis remained unaffected. An increased expression of p53 and SIRT1 with donor age was correlated to their ability of eliminating tumorigenic events through apoptosis or autophagy, respectively. Irrespective of donor age, GMSCs displayed effective immunoregulation and regenerative potential in a mouse model of LPS-induced acute lung injury. Thus, we suggest the potential of GMSCs for designing cell-based immunomodulatory therapeutic approaches and their further extrapolation for acute inflammatory conditions such as acute respiratory distress syndrome and COVID-19.
衰老是间充质干细胞（MSCs）数量和质量下降的原因，这会影响它们在再生医学中的治疗用途。缺乏与年龄相关的干细胞研究进一步限制了它们的临床应用。本研究探讨了从人牙龈组织（GMSCs）中获得的 MSCs 用于研究其体外生长特性和分化潜能与供体年龄的关系的可能性。GMSCs 表现出体外脂肪生成减少以及体外和体内成骨减少，但体外神经发生不受影响。随着供体年龄的增加，p53 和 SIRT1 的表达增加，这与它们通过细胞凋亡或自噬分别消除致瘤事件的能力相关。无论供体年龄如何，GMSCs 在 LPS 诱导的急性肺损伤小鼠模型中均表现出有效的免疫调节和再生潜力。因此，我们建议 GMSCs 具有设计基于细胞的免疫调节治疗方法的潜力，并进一步将其用于急性炎症情况，如急性呼吸窘迫综合征和 COVID-19。
