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

Abstract

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.