Department of Pharmacology, School of Pharmacy Drug Discovery Research Center of Southwest Medical University, and Laboratory for Cardiovascular Pharmacology, Southwest Medical University, Luzhou, Sichuan, China.
Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Southwest Medical University, Luzhou, China.
Cell Commun Signal. 2023 Jun 19;21(1):146. doi: 10.1186/s12964-023-01152-x.
Mesenchymal stem cells (MSCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cells following cell delivery remain critical hurdles for clinical investigation due to the senescence of freshly isolated cells and extensive in-vitro passage.
Cultured adipose-derived stem cells (ASCs) were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, real-time PCR, and Westernblot to evaluate the levels related to cellular senescence markers.
The mRNA expression levels of senescence markers were significantly increased in the later passage of ASCs. We show that light activation reduced the expression of senescent genes, and SA-β-Gal in all cells at passages. Moreover, the light-activated ASCs-derived exosomes decrease the expression of senescence, and SA-β-Gal in the later passage cells. We further investigated the photoreceptive effect of Opsin3 (Opn3) in light-activated ASCs. Deletion of Opn3 abolished the differences of light activation in reduced expression of senescent genes, increased Ca influx, and cAMP levels.
ASCs can undergo cellular senescence in-vitro passage. Photomodulation might be better preserved over senescence and Opn3-dependent activation in aged ASCs. Light-activated ASCs-derived exosomes could be served as e a new protective paradigm for cellular senescence in-vitro passage. Video Abstract.
间充质干细胞（MSCs）疗法作为一种有前途的治疗再生方法正在出现。由于新鲜分离细胞的衰老和广泛的体外传代，细胞递送后治疗的持久性和功能干细胞减少仍然是临床研究的关键障碍。
从正常饮食喂养的小鼠的皮下白色脂肪组织中分离培养脂肪来源的干细胞（ASCs）。我们进行衰老相关-β-半乳糖苷酶（SA-β-gal）染色、实时 PCR 和 Western blot 以评估与细胞衰老标志物相关的水平。
ASCs 后期传代中衰老标志物的 mRNA 表达水平显著增加。我们表明，光激活降低了所有细胞中衰老基因的表达和 SA-β-gal。此外，光激活的 ASC 衍生的外泌体降低了后期传代细胞中衰老和 SA-β-gal 的表达。我们进一步研究了 Opsin3（Opn3）在光激活 ASC 中的光反应性。Opn3 的缺失消除了光激活在降低衰老基因表达、增加 Ca2+内流和 cAMP 水平方面的差异。
ASCs 在体外传代中可以发生细胞衰老。光调节可能比衰老和 Opn3 依赖性激活更好地保留在老年 ASCs 中。光激活的 ASC 衍生的外泌体可作为体外传代细胞衰老的一种新的保护范例。视频摘要。
