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. Transplantation (Tp) of hematopoietic stem cells (HSCs) in Osteogenesis imperfecta (OI) mice causes replacement of mutated osteoblasts with normal osteoblasts (derived from HSCs) that lay down normal collagen and result in clinical improvements.