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

Abstract

Background: Mesenchymal stem/stromal cells (MSCs) can replenish the aged cells of the musculoskeletal system in adult life. Stem cell exhaustion and decrease in their regenerative potential have been suggested to be hallmarks of aging. Here, we investigated whether muscle-and bone-derived MSCs of patients with osteoarthritis and osteoporosis are affected by this exhaustion, compared to healthy donors. Methods: Patients with primary osteoarthritis, femoral neck fractures due to osteoporosis, and healthy donors (controls) were included. MSCs were isolated from the skeletal muscle and subchondral bone from each patient and compared using ex vivo and in vitro analyses, including immunophenotyping, colony-forming unit fibroblast assays, growth kinetics, cell senescence, multilineage potential, and MSC marker gene expression profiling. Results: Freshly isolated cells from muscle from patients with osteoarthritis showed a lower proportion of CD45/ CD19/CD14/CD34-negative cells compared to patients with osteoporosis and healthy donors. Freshly isolated muscle cells from patients with osteoarthritis and osteoporosis also showed higher clonogenicity compared to healthy donors. MSCs from both tissues of osteoarthritis patients showed significantly reduced osteogenesis and MSCs from the bone also reduced adipogenesis. Chondrogenic pellet diameter was reduced in bone-derived MSCs from both patient groups compared to healthy donors. A significant positive correlation was observed between adipogenesis and CD271 expression in muscle-derived MSCs. CD73 was significantly lower in bone-derived MSCs from osteoarthritis patients, compared to osteoporosis patients. Gene expression profiling showed significantly lower expression of MSC marker gene leptin receptor, LEPR, previously identified as the major source of the bone and adipocytes in the adult bone marrow, in bone-derived MSCs from patients with osteoarthritis in comparison with osteoporotic patients and healthy donors.

Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

“…Trivedi et al 36 compared the properties of BMSCs from different swine donors and found that their morphology, growth rate and trilineage differentiation potential were quite different from each other even though they shared comparable expression of some cell surface markers. In addition, Čamernik et al 37 observed that compared to those from healthy donors, bone-derived MSCs from osteoarthritis (OA) patients displayed a reduced trilineage differentiation potential, as well as significantly lower expression of CD73 and leptin receptors.

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Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells

“…In the multivariable analysis model, the absence of osteoporosis and intake of vitamin D supplementation were significant predictors for enhanced OB differentiation outcome. Based on a number of previous studies, the effect of osteoporosis, on in vitro mineralized matrix formation has not been consistent with some studies reporting no effect [ 51 ] or reduced OB differentiation [ 52 – 54 ] when comparing cultured hBMSCs isolated from osteoporotic donors and controls. We have also previously reported that hBMSC cultures established from osteoporotic patients exhibited similar proliferation and differentiation capacities as age-matched controls [ 39 , 46 ].…”

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

“…In addition to inflammation and age-related changes in MSC discussed before, it has also been suggested that their phenotype is affected by specific disease environments, such as osteoporosis, or OA (Egermann et al, 2010 ; Benisch et al, 2012 ; Camernik et al, 2020 ). Based on the evidence that the protein cargo of EVs reflects the pathophysiological status of the parental cells (Mianehsaz et al, 2019 ), it can be assumed that these traits are transferred to the derived EVs, and this has to be considered when choosing the MSC source for EV production.…”