Impact of aging on the regenerative properties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells.

Impact of aging on the regenerative properties of bone marrow-, muscle-, and adipose-derived mesenchymal stem/stromal cells.
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DOI:
10.1371/journal.pone.0115963
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Darling EM
Darling EM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Beane OS;Fonseca VC;Cooper LL;Koren G;Darling EM

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间充质干细胞/基质细胞(MSC)由于其多能性和现成的可用性,是再生疗法的有前途的细胞来源,但其应用可能会因患者特定因素(如年龄或疾病)而复杂化。已经研究了MSC用于治疗许多肌肉骨骼疾病,包括骨关节炎和骨质疏松症。由于这些疾病在老年人群中的流行,研究人员研究了衰老如何影响MSC的特性,并发现增殖和分化潜力受损。然而,这些效果从未在从同一健康供体的多种组织来源分离的MSC之间进行过比较。揭示MSC如何受年龄影响的差异可能有助于确定针对老年患者的肌肉骨骼疗法的最佳细胞来源。从年轻和老年兔的骨髓、肌肉和脂肪组织中分离MSC。分离程序后定量细胞产量和活力,并使用增殖、衰老和集落形成测定法评估扩增特性。还使用谱系特异性染色和代谢物分光光度法检查了多能性。结果进行了比较,年龄组之间和MSC的来源。结果显示,MSC受到老化的不同影响,骨髓来源的干细胞具有受损的增殖,衰老和软骨形成反应,而肌肉来源的干细胞和脂肪来源的干细胞没有表现出负面影响。虽然年龄降低了所有MSC群体的总细胞产量和成脂潜力,但成骨和克隆形成保持不变。这些发现表明,在为老年患者设计基于细胞的疗法时,年龄是一个重要因素。
Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative therapies due to their multipotency and ready availability, but their application can be complicated by patient-specific factors like age or illness. MSCs have been investigated for the treatment of many musculoskeletal disorders, including osteoarthritis and osteoporosis. Due to the prevalence of these diseases in older populations, researchers have studied how aging affects MSC properties and have found that proliferation and differentiation potential are impaired. However, these effects have never been compared among MSCs isolated from multiple tissue sources in the same, healthy donor. Revealing differences in how MSCs are affected by age could help identify an optimal cell source for musculoskeletal therapies targeting older patients. MSCs were isolated from young and old rabbit bone marrow, muscle, and adipose tissue. Cell yield and viability were quantified after isolation procedures, and expansion properties were assessed using assays for proliferation, senescence, and colony formation. Multipotency was also examined using lineage-specific stains and spectrophotometry of metabolites. Results were compared between age groups and among MSC sources. Results showed that MSCs are differentially influenced by aging, with bone marrow-derived stem cells having impaired proliferation, senescence, and chondrogenic response, whereas muscle-derived stem cells and adipose-derived stem cells exhibited no negative effects. While age reduced overall cell yield and adipogenic potential of all MSC populations, osteogenesis and clonogenicity remained unchanged. These findings indicate the importance of age as a factor when designing cell-based therapies for older patients.
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