Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cells.

Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cells.
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DOI:
10.1016/j.joca.2010.01.011
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发表时间:
2010-05
影响因子:
7
通讯作者:
Chu, C. R.
Chu, C. R.
中科院分区:
医学2区
文献类型:
--
作者:
Payne, K. A.;Didiano, D. M.;Chu, C. R.

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受损的关节软骨无法很好地愈合,并可能发展为骨关节炎 (OA)。人骨髓干细胞(BMC)是用于关节软骨修复的有希望的细胞,但其软骨形成中与年龄和性别相关的差异尚未明确确定。本研究的目的是测试人类股骨 BMC 的软骨形成潜力是否因供体的性别和/或年龄而异。在骨科手术过程中,从 21 名男性(16-82 岁)和 20 名女性(20-77 岁)中分离出 BMC。在存在或不存在 TGFβ1 的情况下,通过标准沉淀培养测定法测量累积群体倍增 (CPD) 并评估软骨形成。测量沉淀面积,并通过甲苯胺蓝和番红 O-快绿组织学分级,使用 Bern 评分和糖胺聚糖 (GAG) 含量来确定软骨形成分化。没有观察到由于捐赠者性别或年龄而导致的 CPD 差异。在男性 BMC 中,添加 TGFβ1 后颗粒面积的增加和 Bern 评分随着供体年龄的增加而显着降低,但在女性 BMC 中则不然。随着雄性 BMC 供体年龄的增加,每个颗粒的 GAG 含量也显着降低。在女性 BMC 中没有观察到这一点。这项研究表明,在男性 BMC 中,TGFβ1 刺激后,软骨样分化会出现与年龄相关的下降,但在女性 BMC 中则不然。了解这些差异的机制将有助于改善自体 BMC 在关节软骨修复中的临床应用,并可能导致开发基于年龄或性别的定制治疗方法,以延迟或预防 OA 的发病。
Damaged articular cartilage does not heal well and can progress to osteoarthritis (OA). Human bone marrow stem cells (BMC) are promising cells for articular cartilage repair, yet age- and sex-related differences in their chondrogenesis have not been clearly identified. The purpose of this study is to test whether the chondrogenic potential of human femoral BMC varies based on the sex and/or age of the donor. BMC were isolated from 21 males (16–82 y.o.) and 20 females (20–77 y.o.) during orthopaedic procedures. Cumulative population doubling (CPD) was measured and chondrogenesis was evaluated by standard pellet culture assay in the presence or absence of TGFβ1. Pellet area was measured, and chondrogenic differentiation was determined by Toluidine Blue and Safranin O-Fast Green histological grading using the Bern score and by glycosaminoglycan (GAG) content. No difference in CPD was observed due to donor sex or age. The increase in pellet area with addition of TGFβ1 and the Bern score significantly decreased with increasing donor age in male BMC, but not in female BMC. A significant reduction in GAG content per pellet was also observed with increasing donor age in male BMC. This was not observed in female BMC. This study showed an age-related decline in chondroid differentiation with TGFβ1 stimulation in male BMC, but not in female BMC. Understanding the mechanisms for these differences will contribute to improved clinical use of autologous BMC for articular cartilage repair, and may lead to the development of customized age- or sex-based treatments to delay or prevent the onset of OA.
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