Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

Abstract

ObjectiveIn patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non‐BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences.MethodsEx vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI‐determined BML and non‐BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony‐forming unit–fibroblast (CFU‐F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture‐expanded CD271+ cells were analyzed for tripotentiality and gene expression.ResultsBML regions were associated with greater trabecular bone area and cartilage damage compared with non‐BML regions. The proportion of CD45−CD271+ MSCs was higher in BML regions compared with non‐BML regions (median difference 5.6‐fold; P < 0.001); the CFU‐F assay showed a similar trend (median difference 4.3‐fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell–derived factor 1 receptor. OA MSCs showed up‐regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone.ConclusionThis study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target.

Murine Rankl−/− Mesenchymal Stromal Cells Display an Osteogenic Differentiation Defect Improved by a RANKL-Expressing Lentiviral Vector

“…On the other hand, to the best of our knowledge the possibility that the expression level of this cytokine might influence the stromal compartment itself in physiopathological conditions has not been clearly addressed yet. In a recent article, Campbell and colleagues found a reduced mineralization capacity concomitantly with lower RANKL gene expression in MSCs from BM lesions of late stage osteoarthritic patients . Other authors observed an increase in RANKL expression together with reduced bone mineralization during osteogenic differentiation of MSC lines established from aged (72 weeks old) mice .…”

Comprehensive analysis of skeletal muscle- and bone-derived mesenchymal stem/stromal cells in patients with osteoarthritis and femoral neck fracture

“…Both OA and OP are age-related, and stem cell exhaustion and decreases in their regenerative potential have been defined as one of the hallmarks of aging [7]. Previous studies have shown reduced chondrogenic potential of bone marrow-derived MSCs, with further other alterations to these cells that are implicated in the emergence of OA [8,9]. OP, on the other hand, has been defined as "obesity of the bone," as bone marrow-derived MSCs are redirected from osteogenesis to adipogenesis [5,6].…”

“…The bone marrow is the most common source for these cell therapies. However, based on previous findings, the bone marrow might not be ideal, as their MSCs can be affected by the concomitant disorder; in particular OA or OP [5,8,9]. The skeletal muscle, on the other hand, is an untapped reservoir of MSCs [17].…”

Modulation of Synovial Fluid‐Derived Mesenchymal Stem Cells by Intra‐Articular and Intraosseous Platelet Rich Plasma Administration

“…Although the source of MSCs has not been yet clearly determined, the most likely origin might be the SM [4, 5], the breakdown zone of superficial AC, and the SB [6, 9, 10]. Recent findings suggest that the increase in pathological situations of certain molecules such as monocyte chemotactic protein-1, SDF-1, and TGF- β 1 could promote the recruitment of MSCs [11, 12]. …”