Stem Cells Harvested from Bone Marrow and Adipose Tissue Demonstrate Differential Healing Mechanisms and Union Rates in a Murine Model of Irradiated Mandibular Fracture Repair
Kavitha Ranganathan, M.D., Alexandra Luby, BS, Noah Nelson, BS, Alicia Snider, MD, Alexis Donneys, MD, Russell Ettinger, MD, Joseph Rodriguez, MD, Shuli Li, PhD, Lauren Buchman, N/A, Benjamin Levi, MD, Steven R. Buchman, MD.
University of Michigan Health Systems, Ann Arbor, MI, USA.
PURPOSE: The accessibility of adipose-derived stromal cells (ASCs) over bone marrow stromal cells (BMSCs) warrants investigation into their utility for bone healing. The goal of this study was to compare the mechanisms through which ASCs and BMSCs exert their effect on fracture healing. We hypothesize that ASCs will enhance fracture healing by improving vasculogenesis, while BSMCs will directly affect osteogenesis.
METHODS: Lewis rats were radiated (35Gy) and underwent mandibular osteotomy with implantation of BMSCs (n=12) or ASCs (n=16) marked with Green fluorescent protein (GFP). MicroCT and Confocal microscopy evaluated 40-day union rates and the contribution of ASCs/BMSCs to the bone regenerate. Quantitative PCR of ASCs/BMSCs compared expression of osteogenic and vasculogenic genes. Co-culture of ASCs (n=3) or BMSCs (n=3) with human umbilical vein endothelial cells (HUVECs) was performed to measure tubule formation/vasculogenesis.
RESULTS: ASC-implantation resulted in higher union rates than BMSC-implantation (94% vs. 66%), and contributed indirectly to fracture healing, as GFP was not visualized. (Fig. 1A) BMSCs expressed osteogenic genes to a significantly greater degree than did ASCs. (1B) ASCs expressed greater levels of VEGF, translating into greater tubule formation among co-cultured HUVECs (64.3±7.3 vs. 23.3±2.6; p=0.0008). (1C)
CONCLUSIONS: ASCs heal fractures better than BMSCs, likely through indirect modulation of vasculogenesis, rather than osteogenesis. ASCs may be a promising clinical option for radiation-induced fracture repair, given their accessibility and improved fracture healing.
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