Abstract
Currently, there is no cure for Osteogenesis imperfecta (OI) - a debilitating pediatric skeletal dysplasia. Herein we show that hematopoietic stem cell (HSC) therapy holds promise in treating OI. Using single cell HSC transplantation in lethally irradiated oim/oim mice, we demonstrate significant improvements in bone morphometric, mechanics and turnover parameters. Importantly, we highlight that HSCs cause these improvements due to their unique property of differentiating into osteoblasts/osteocytes, depositing healthy collagen- an attribute thus far assigned only to mesenchymal stem cells. To confirm this HSC plasticity, lineage tracing was done by transplanting oim/oim with HSCs from two specific transgenic mice - VavR, in which all hematopoietic cells are GFP + and pOBCol2.3GFP, where GFP is expressed only in osteoblasts/osteocytes. In both models, transplanted oim/oim mice demonstrated presence of GFP + HSC-derived osteoblasts/osteocytes in bones. These studies unequivocally establish that HSCs differentiate into osteoblasts/osteocytes and HSC transplantation can provide a new translational approach for OI.
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