Bone formation and optimal bone regeneration by using adult stem cells and endothelial progenitor cells and analysis of the molecular mechanism

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Human mesenchymal stem cells (hMSC) and osteogenic cytokines (Bone Morphogenetic Protein-2, BMP-2 and basic Fibroblast Growth Factor, bFGF) form and regenerate in cranial defect and in ectopic vascularized flao with a gelatin carrier as a scaffold. Regenerated bone is regulated by "mesenchymal" lineage by transcription factor in four weeks after transplantation. The bFGF enhances angiogenesis and flap blood flow as well as increases hMSC proliferation. The Green Fluorescent Protein (GFP)-transfected hMSC demonstrated transcription factor, PEB2a, expression by day 7 along with GFP-positive cells and mature bone cell marker, osteocalcin, by day 14 diffusely along with GFP-positive cells. This explains the grafted hMSCs differentiated into bone. The cells, materials, and chemical factors are all either clinically approved or eligible in the near future in Japan since at least all are approved in USA and European nations. This may be leading to mesenchymal stem cell bone regeneration in the clinical application. More data with non-human primates may be required for orthotopic and ectopic bone regeneration experiments.