Development of a new treatment for osteoporotic vertebral fractures using adipose-derived stem cell spheroids.

AIMS: Osteoporotic vertebral fractures substantially contribute to disability and often require surgical intervention. However, some challenges, such as implant failure and suboptimal bone regeneration, limit current treatments. Adipose-derived stem cells are promising for regenerative therapy because they are easily obtained, highly proliferative, and resistant to osteoporosis-related symptoms. This study aimed to evaluate the combined effects of osteogenic adipose-derived stem cell spheroids and β-tricalcium phosphate on vertebral bone regeneration in a rat osteoporotic vertebral fracture model. METHODS: Osteoporosis was induced in 33 rats (11 per group) by ovariectomy, and defects were created in the L4 and L5 vertebrae. Adipose-derived stem cells were spheroidized and mixed with β-tricalcium phosphate scaffolds. Groups included osteogenic spheroids, undifferentiated spheroids, and β-tricalcium phosphate alone. Bone regeneration was assessed using micro-CT, histology, and biomechanical testing at four and eight weeks. Further in vitro analyses were conducted. RESULTS: The osteogenic spheroid group showed significantly higher bone mass, fusion score, and mechanical strength than the control group did. Histological analysis revealed enhanced new bone formation and β-tricalcium phosphate integration. Gene expression analysis revealed osteogenic marker (alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor 2 (Runx2)) and regenerative factor (bone morphogenetic protein 7 (BMP-7), insulin-like growth factor 1 (IGF-1), hepatocyte growth factor 1 (HGF-1), and octamer-binding transcription factor4 (Oct4) upregulation, along with reduced apoptosis. Further, adipose-derived stem cell survival was confirmed at the repair site. These results indicate that adipose-derived stem cells contribute to both paracrine and direct osteogenesis. CONCLUSION: Combining osteogenic adipose-derived stem cell spheroids with β-tricalcium phosphate scaffolds effectively promotes vertebral bone regeneration in osteoporotic vertebral fracture. This approach is a promising strategy for improving osteoporotic fracture repair with potential clinical applications.