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1.  Induction of Fracture Repair by Mesenchymal Cells Derived from Human Embryonic Stem Cells or Bone Marrow 
Development of novel therapeutic approaches to repair fracture non-unions remains a critical clinical necessity. We evaluated the capacity of human embryonic stem cell (hESC)-derived mesenchymal stem/stromal cells (MSCs) to induce healing in a fracture non-union model in rats. In addition, we placed these findings in the context of parallel studies using human bone marrow MSCs (hBM-MSCs) or a no cell control group (n = 10 to 12 per group). Preliminary studies demonstrated that both for hESC-derived MSCs and hBM-MSCs, optimal induction of fracture healing required in vitro osteogenic differentiation of these cells. Based on biomechanical testing of fractured femurs, maximum torque and stiffness were significantly greater in the hBM-MSC as compared to the control group that received no cells; values for these parameters in the hESC-derived MSC group were intermediate between the hBM-MSC and control groups, and not significantly different from the control group. However, some evidence of fracture healing was evident by X-ray in the hESC-derived MSC group. Our results thus indicate that while hESC-derived MSCs may have potential to induce fracture healing in non-unions, hBM-MSCs function more efficiently in this process. Additional studies are needed to further modify hESCs to achieve optimal fracture healing by these cells.
PMCID: PMC3179810  PMID: 21674605
embryonic stem cells; mesenchymal stem/stromal cells; osteogenic; bone repair; fracture non-union
2.  Augmentation of Surgical Angiogenesis in Vascularized Bone Allotransplants with Host-Derived AV Bundle Implantation, Fibroblast Growth Factor-2 and Vascular Endothelial Growth Factor Administration 
We have previously shown experimental transplantation of living allogeneic bone to be feasible without long-term immunosuppression by development of a recipient-derived neoangiogenic circulation within bone. In this study we study the role of angiogenic cytokine delivery with biodegradable microspheres to enhance this process. Microsurgical femoral allotransplantation was performed from DA to PVG rats. Poly(D,L-lactide-co-glycolide) microspheres loaded with buffer, basic fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), or both were inserted intramedullarly along with a recipient-derived a/v bundle. FK-506 was administered daily for 14 days, then discontinued. At 28 days, bone blood flow was measured using hydrogen washout. Microangiography, histologic and histomorphometric analysis were performed. Capillary density was greater in the FGF+VEGF group (35.1%) than control (13.9%) (p<0.05), and a linear trend was found from control, FGF, VEGF, to FGF+VEGF (p<0.005). Bone formation rates were greater with VEGF (p<0.01) and FGF+VEGF (p<0.05). VEGF or FGF alone increased blood flow more than when combined. Histology rejection grading was low in all grafts. Local administration of vascular and fibroblast growth factors augments angiogenesis, bone formation and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts after removal of immunosuppression.
PMCID: PMC2892011  PMID: 20162714
bone; allotransplantation; microspheres; FGF; VEGF

Results 1-2 (2)