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

Abstract

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.