幹細胞研究と治療のジャーナル

概要

In vivo Effects of Bioactive Glass S53P4 or Beta Tricalcium Phosphate on Osteogenic Differentiation of Human Adipose Stem Cells after Incubation with BMP-2

Martin Waselau, Mimmi Patrikoski, Bettina Mannerström, Mari Raki, Kim Bergström, Brigitte von Rechenberg and Susanna Miettinen

Aims: Human adipose stem cells (hASCs) have been suggested as viable alternative for bone tissue engineering. However, the tissue response and osteogenic potential of BAG S53P4 or β-TCP granules has not been studied in vivo when seeded with hASCs and/or co-incubated with BMP-2 and thus, was evaluated in the current study.

Methods and results: Human ASCs were isolated, expanded and seeded on BAG and β-TCP in vitro and, cell viability was assessed using Live/Dead staining. In a subcutaneous rodent implantation model, the cellular response and osteogenic potential of 1) plain, 2) hASC seeded, 3) BMP-2 co-incubated and 4) hASC seeded and BMP-2 co-incubated BAG and β-TCP granules were investigated using computed tomography and semi-quantitative histologic scores after 4 and 8 weeks. Live/Dead staining confirmed good cell viability on both biomaterials prior to implantation. Overall, implantation of both biomaterials resulted in formation of well-vascularized granulation tissue without excessive inflammation, fibrosis or adverse reactions independent on group assignment and time point evaluated and thus, suggesting safety for prospective applications. However, our results also indicate that β-TCP may temporarily stimulate foreign body giant cell formation after hASCs supplementation suggesting a resorptive response. Both biomaterials required supplementation of hASCs and/or BMP-2 to induce osteoblastic
activity. However, BAG induced calcification exclusively when seeded with BMP-2 activated hASCs, whereas β-TCP required seeding with hASCs only.

Conclusion: BAG and β-TCP granules can be safely implanted subcutaneously, induce a different cellular response and require hASC and/or BMP-2 supplementation to induce osteoblastic activity and calcification. A combination of β-TCP and hASCs appeared to be a feasible way in enhancing osteoblastic activity resulting in early osteogenesis while minimizing safety and regulatory concerns in bone-tissue engineering.