Cartilage Restoration Center, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Osteoarthritis Cartilage. 2010 May;18(5):705-13. doi: 10.1016/j.joca.2010.01.011. Epub 2010 Feb 6.
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 years old (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 transforming growth factor beta 1 (TGFbeta1). 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 TGFbeta1 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 TGFbeta1 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.
受损的关节软骨愈合不佳，可进展为骨关节炎（OA）。人骨髓基质细胞（BMC）是关节软骨修复有前途的细胞，但它们的软骨生成能力与年龄和性别相关的差异尚未明确确定。本研究旨在测试供体的性别和/或年龄是否会影响人股骨 BMC 的软骨形成潜力。
在骨科手术期间，从 21 名男性（16-82 岁）和 20 名女性（20-77 岁）中分离 BMC。通过标准的微球体培养测定法评估累积群体倍增（CPD）和软骨生成，在存在或不存在转化生长因子β 1（TGFβ1）的情况下进行。测量微球体的面积，并通过甲苯胺蓝和Safranin O-Fast 绿组织学分级（使用 Bern 评分）和糖胺聚糖（GAG）含量来确定软骨分化。
由于供体的性别或年龄，CPD 没有差异。在添加 TGFβ1 后，微球体面积的增加以及 Bern 评分随着男性 BMC 供体年龄的增加而显著降低，但女性 BMC 中则没有。男性 BMC 中，每个微球体的 GAG 含量也随着供体年龄的增加而显著降低。在女性 BMC 中则没有观察到这种情况。
本研究表明，男性 BMC 中存在与 TGFβ1 刺激相关的软骨分化随年龄增长而下降的现象，但女性 BMC 中则没有。了解这些差异的机制将有助于改进自体 BMC 用于关节软骨修复的临床应用，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 的发生。
