Čamernik Klemen, Mihelič Anže, Mihalič Rene, Marolt Presen Darja, Janež Andrej, Trebše Rihard, Marc Janja, Zupan Janja
University of Ljubljana, Faculty of Pharmacy, Department of Clinical Biochemistry, Askerceva 7, Ljubljana 1000, Slovenia.
Valdoltra Orthopaedic Hospital, Jadranska 31, Ankaran, SI 6280, Slovenia.
Stem Cell Res. 2019 Jul;38:101465. doi: 10.1016/j.scr.2019.101465. Epub 2019 May 14.
Mesenchymal stem/stromal cells (MSCs) are being exploited for patient-derived stem-cell therapies. As the biological properties of MSCs derived from skeletal muscle of osteoarthritis patients are poorly understood, the aim of this study was to compare muscle MSCs with well-recognized bone and bone marrow-derived MSCs from these patients. Paired samples of skeletal muscle and trabecular bone tissue were obtained from 21 patients with osteoarthritis. Isolated cells were compared using ex vivo immunophenotyping and detailed in vitro analyses. These included the colony forming unit fibroblast assay, growth kinetics, senescence, multilineage potential, immunophenotyping, and MSC marker gene expression profiling. Freshly isolated MSCs from muscle showed improved viability over bone-derived MSCs, with similar mesenchymal fraction. Muscle-derived MSCs showed superior clonogenicity, higher growth rates, and lower doubling times. Muscle-derived MSCs also showed superior osteogenic and myogenic properties and a positive correlation between CD271 expression and adipogenesis. Senescence rate as well as adipogenic and chondrogenic potentials were similar. Skeletal muscle-derived MSCs of osteoarthritis patients have superior clonogenicity and growth kinetics compared to bone-derived MSCs, making them a good candidate for autologous stem-cell therapies. Moreover, the positive correlation between CD271 and adipogenesis suggest that CD271 expressing muscle MSCs might contribute to muscle steatosis observed in osteoarthritis.
间充质干/基质细胞(MSCs)正被用于患者来源的干细胞治疗。由于对骨关节炎患者骨骼肌来源的MSCs的生物学特性了解甚少,本研究的目的是将肌肉来源的MSCs与这些患者中公认的骨和骨髓来源的MSCs进行比较。从21例骨关节炎患者中获取骨骼肌和松质骨组织的配对样本。使用体外免疫表型分析和详细的体外分析对分离的细胞进行比较。这些分析包括集落形成单位成纤维细胞测定、生长动力学、衰老、多向分化潜能、免疫表型分析和MSCs标记基因表达谱分析。新鲜分离的肌肉来源的MSCs比骨来源的MSCs具有更高的活力,间充质分数相似。肌肉来源的MSCs表现出更高的克隆形成能力、更高的生长速率和更短的倍增时间。肌肉来源的MSCs还表现出 superior osteogenic and myogenic properties and a positive correlation between CD271 expression and adipogenesis. 衰老率以及成脂和成软骨潜能相似。与骨来源的MSCs相比,骨关节炎患者骨骼肌来源的MSCs具有更高的克隆形成能力和生长动力学,使其成为自体干细胞治疗的良好候选者。此外,CD271与脂肪生成之间的正相关表明,表达CD271的肌肉MSCs可能与骨关节炎中观察到的肌肉脂肪变性有关。 (原文中superior osteogenic and myogenic properties部分表述似乎不完整,翻译时保留原文形式)