ArticleBMC musculoskeletal disorders2026
Evaluation of mesenchymal stem cells' bone repair capacity via osteogenic lineage differentiation in experimental nonunion fractures.
Article in BMC musculoskeletal disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNonunion of fractures is a major challenge in orthopedics and traumatology, especially with increasing high-energy injuries. Adipose-derived mesenchymal stem cells (ASCs) are a readily accessible source with strong osteogenic potential. This study compared the bone regenerative efficacy of undifferentiated ASCs versus their osteogenically pre-differentiated derivatives in a critical-size femoral nonunion model.
methodsEighteen male New Zealand White rabbits (n = 18), aged 3 months and weighing 2.94 ± 0.10 kg, were included. MSCs were isolated enzymatically from abdominal adipose tissue of three donor rabbits. At passage 3, cells were cultured either in basal medium (undifferentiated cohort) or osteogenic medium containing β-glycerophosphate, dexamethasone, and ascorbic acid for 4 weeks (differentiated cohort). 5-bromo-2'-deoxyuridine solution (BrdU) labeling was performed. In this randomized controlled in vivo study, a 5-mm mid-femoral defect was created and stabilized with angular-stable plating. In this randomized, controlled in vivo experimental study, on postoperative day 7 the animals were allocated to three groups (n = 5 per group): control (defect alone), undifferentiated mesenchymal stem cells, and differentiated mesenchymal stem cells. Radiographic assessment of bridging callus and cortical thickness index was performed at 4 and 6 weeks; serum total protein, calcium, and alkaline phosphatase were measured.
resultsIn vitro, osteogenic differentiation induced progressive mineralization (Alizarin Red staining) and a statistically significant 34% reduction in BrdU corrected total cell fluorescence (CTCF) (p = 0.0473). In vivo, both cell-augmented groups accelerated fracture consolidation versus controls. The differentiated cohort achieved 88% bridging callus at 6 weeks (versus 80% in the undifferentiated group), with superior improvements in bridged cortices (+ 9.4%), bridging callus coverage (+ 10.0%), and distal gap closure (-31.0%) at 6 weeks, plus more pronounced cortical remodeling (average CTI decrease - 6.2% at 4 weeks). Serum alkaline phosphatase (ALP) declined by 53.4% (undifferentiated) and 63.6% (differentiated) versus control (both p < 0.001); plasma calcium was 16.8% higher in the undifferentiated group. Immunofluorescence showed 19% higher BrdU-positive cell density and 12% higher CTCF in undifferentiated cells.
conclusionsOsteogenically pre-differentiated ASCs demonstrated enhanced bone regenerative capacity compared with undifferentiated ASCs. These findings indicate that osteogenic pre-differentiation augments the therapeutic potential of ASCs and support their further evaluation in multimodal strategies for fracture nonunion.
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