Donor ethnicity, sex, and age impact chondrogenic re-differentiation capacity: a multi-demographic study of human articular chondrocytes in vitro

Abstract

ABSTRACT To unravel causes of disparities in osteoarthritis (OA) prevalence and to improve cell-based cartilage repair treatments, there is need to investigate the multifactorial impact of patient demographics on a biophysiological level. In this study, we systematically analyse single- and multi-demographic impact on in vitro chondrogenic re-differentiation capacity of human articular chondrocytes (hACs), specifically of an Aotearoa-New Zealand (NZ) patient cohort which displays unique demographic diversity. HACs were isolated from 14 NZ donors with distinct demographics (ethnicity: indigenous Māori vs European descendant Pākehā; sex; age 18–24 vs 25–30 yrs). In vitro chondrogenic re-differentiation capacity of donor chondrocytes was assessed through quantifications of cartilage matrix deposition (GAG, DNA, GAG/DNA) and by histological visualisation. Isolated chondrocytes ranged from low chondrogenic re-differentiation capacity, characterised by fibrocartilage tissue deposition, to high re-differentiation capacity to deposit GAG-rich tissue. Age-related reduction in GAG/DNA content was detected while no impact of ethnicity or sex was observed. Multi-demographic analysis revealed reduced GAG deposition in Māori male (compared to Māori female), and Māori (18–24 yrs) compared to Māori (25–30 yrs) and Pākehā (18–24 yrs) within our cohort. Multi-demographic analysis is a promising strategy to understand disparities in OA prevalence in patient cohorts and can help guide development of cell-based strategies for diverse patient populations.