Changes in Chondrogenic Progenitor Populations Associated with Aging and Osteoarthritis

Abstract

Chondrogenic progenitor populations, including mesenchymal stem cells, represent promising cell-based transplantation or tissue engineering therapies for the regeneration of damaged cartilage. Osteoarthritis (OA) predominantly affects the elderly and is a leading cause of disability worldwide. Advancing age is a prominent risk factor that is closely associated with the onset and progression of the disease. Understanding the influence that aging and OA have on chondrogenic progenitor cells is important to determine how these processes affect the cellular mechanisms of the cells and their capacity to differentiate into functional chondrocytes for use in therapeutic applications. Here, we review the effect of age-and OA-related changes on the growth kinetics and differentiation potential of chondrogenic progenitor cell populations. Aging differentially influences the proliferative potential of progenitor cells showing reduced growth rates with increased senescence and apoptotic activity over time, while chondrogenesis appears to be independent of donor age. Cartilage tissue affected by OA shows evidence of progenitor populations with some potential for repair, however reports on the proliferative propensity of mesenchymal stem cells and their chondrogenic potential are contradictory. This is likely attributed to the narrow age ranges of samples assessed and deficits in definitively identifying donors with OA versus healthy patients across a wide scope of advancing ages. Further studies that investigate the mechanistic effects of chondrogenic progenitor populations associated with aging and the progression of OA using clearly defined criteria and age-matched control subject groups are crucial to our understanding of the clinical relevance of these cells for use in cartilage repair therapies.

Significance of MEF2C and RUNX3 Regulation for Endochondral Differentiation of Human Mesenchymal Progenitor Cells

“…Also, there is no hint in the literature that, vice versa, healthy but not OA chondrocytes would express RUNX2, RUNX3, or MEF2C. Regarding MPCs, we and many other groups have documented that hypertrophy develops irrespective of whether the bone marrow aspirates were derived from OA patients or non-OA patients (Scharstuhl et al, 2007;Dexheimer et al, 2011;Brady et al, 2015). Nevertheless, unless data are repeated with cells from healthy donors, the OA background should be kept in mind.…”

Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression

“…Previous studies have suggested that cells derived from C dp had higher proliferation and differentiation potential in comparison to C sp cells . This difference in observations could be attributed to the disease state of the tissue collected in prior studies, the anatomic site of collection, methods of digestion, and culture conditions …”

“…It should be noted that cartilage specimens assessed in this study exhibited Outerbridge grade 1–2 OA (cartilage with swelling or some small fissures on the surface), and were obtained from an older patient population (age group: 45–76 years). The effect of ageing and OA on adult progenitor population in different zones of cartilage has been scarcely studied, and the limited literature available presents conflicting results . Rolauffs et al has previously reported that cell densities in superficial zone of non‐degenerate (Collins0‐I) and degenerate femoral condyle cartilage (Collins II) were 9.5 million cells per gram, and 15 million cells/gram and significantly differ.…”

“…It is noteworthy that all these studies relied on gene expression, surface marker expression and histological analysis of micromass pellet cultures to identify progenitor cells. However, it has also been challenged that these methods are unable to accurately measure these outcomes …”

“…Prior reports have suggested that the number and the biological performance of the CTPs in knee cartilage is profoundly influenced by several parameters, including (i) zonal location (depth) in the cartilage; (ii) degree of disease progression in the cartilage; and (iii) clinical patient variables . However, many of these associations have been based on CFU assays performed by hand, without the benefit of automated image processing (ASTM standard)…”