Ma Linsha, Hu Jingchao, Cao Yu, Xie Yilin, Wang Hua, Fan Zhipeng, Zhang Chunmei, Wang Jinsong, Wu Chu-Tse, Wang Songlin
1Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University, School of Stomatology, Beijing, China.
2Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
Aging Dis. 2019 Aug 1;10(4):793-806. doi: 10.14336/AD.2018.0729. eCollection 2019 Aug.
Owing to excellent therapeutic potential, mesenchymal stem cells (MSCs) are gaining increasing popularity with researchers worldwide for applications in tissue engineering, and in treatment of inflammation-related and age-related disorders. However, the senescence of MSCs over passaging has limited their clinical application owing to adverse effect on physiological function maintenance of tissues as well as disease treatment. An inflammatory microenvironment is one of the key contributors to MSC senescence, resulting in low regeneration efficiency. Therefore, MSCs with high resistance to cellular senescence would be a benefit for tissue regeneration. Toward this end, we analyzed the senescence properties of different types of stem cells during culture and under inflammation, including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), bone marrow mesenchymal stem cells (BMMSCs), and adipose-derived stem cells (ADSCs). Overall, the DPSCs had higher proliferation rates, lower cellular senescence, and enhanced osteogenesis maintenance compared to those of non-dental MSCs cultured from passage three to six. The expression profiles of genes related to apoptosis, cell cycle, and cellular protein metabolic process (contributing to the cell self-renewal ability and metabolic processes) significantly differed between DPSCs and BMMSCs at passage three. Moreover, DPSCs were superior to BMMSCs with regards to resistance to lipopolysaccharide-induced apoptosis and senescence, with enhanced osteogenesis , and showed improved periodontal regeneration after injection in a miniature pig periodontitis model . Overall, the present study indicates that DPSCs show superior resistance to subculture and inflammation-induced senescence and would be suitable stem cells for tissue engineering with inflammation.
由于具有出色的治疗潜力，间充质干细胞（MSCs）在组织工程以及炎症相关和年龄相关疾病治疗中的应用越来越受到全球研究人员的青睐。然而，MSCs传代后的衰老限制了它们的临床应用，因为这会对组织的生理功能维持以及疾病治疗产生不利影响。炎症微环境是导致MSCs衰老的关键因素之一，会导致再生效率低下。因此，对细胞衰老具有高抗性的MSCs将有利于组织再生。为此，我们分析了不同类型干细胞在培养过程中和炎症条件下的衰老特性，包括牙髓干细胞（DPSCs）、牙周膜干细胞（PDLSCs）、骨髓间充质干细胞（BMMSCs）和脂肪来源干细胞（ADSCs）。总体而言，与传代三至六代培养的非牙髓MSCs相比，DPSCs具有更高的增殖率、更低的细胞衰老水平以及更强的成骨维持能力。在传代三代时，DPSCs和BMMSCs之间与凋亡、细胞周期和细胞蛋白质代谢过程（有助于细胞自我更新能力和代谢过程）相关的基因表达谱存在显著差异。此外，在抗脂多糖诱导的凋亡和衰老方面，DPSCs优于BMMSCs，具有更强的成骨能力，并且在小型猪牙周炎模型中注射后显示出更好的牙周再生效果。总体而言，本研究表明DPSCs对传代培养和炎症诱导的衰老具有卓越的抗性，将是适用于炎症相关组织工程的干细胞。
