Hematopoietic stem cell-derived functional osteoblasts exhibit therapeutic efficacy in a murine model of osteogenesis imperfecta.

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 normal collagen-an attribute thus far assigned only to mesenchymal stem/stromal cells. To confirm 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 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.