Bone regenerative potential of adipose-derived stromal vascular fraction on a xenohybrid bone scaffold




Calcified Tissue International and Musculoskeletal Research, Springer


I. Roato, D. C. Belisario, M. Compagno, L.Verderio, A. Sighinolfi, F. Mussano, T. Genova, F. Veneziano, G. Pertici, G. Perale, R. Ferracini


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Adipose tissue-derived stem cells (ASCs) are a promising tool for treatment of bone diseases or skeletal lesions, thanks to their multilineage differentiating ability. Osteoarthritis, a disease characterized by articular cartilage degeneration and subchondral bone sclerosis, may benefit from non-surgical treatments based on intra-articular infusions of ASCs. One of the major limitations of ASCs is represented by the necessity to be isolated and expanded through in vitro culture, thus a strong interest was generated by the adipose stromal vascular fraction (SVF), the non-cultured fraction of ASCs. We investigated and compared the bone regenerative potential of SVF and ASCs, taking advantage of their ability to grow on Smart-Bone” (SB), a xenohybrid bone scaffold. Both ASCs and SVF colonized and formed new tissue on SB, filling its periphery and bone lacunae over time. At 15, 30 and 60 days, we monitored the tissue growth through immunoistochemical staining: collagen I, osteocalcin and TGFb markedly stained the new tissue on SB. MicroCT analysis showed a progressive increase in mineralised tissue apposition by newly formed trabeculae. Indeed, their quantification analysis demonstrated that SVFs were significantly more efficient than ASCs (3391 ± 270.5 vs. 1825 ± 133.4, p.001) in inducing bone formation, when cultured on SB with osteogenic medium. In SVF cultures, we observed an increased secretion of soluble factors stimulating osteoblasts over time: VEGF (153.5–1278.1 pg/ml) and endothelin 1 (0.43–1.47 pg/ml). In conclusion, the absence of manipulation of SVF in an in vitro culture could definitively represent a benefit for a larger use in clinical applications. Moreover, our data strongly support an innovative idea for a regenerative medicine based on solid scaffold functionalised with SVF to improve the precision of stem cells implant and the quality of new bone formation.




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