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.

中文翻译：

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造血干细胞衍生的功能性成骨细胞在成骨不全小鼠模型中表现出治疗功效

目前，成骨不全症 (OI) 尚无法治愈，这是一种使人衰弱的小儿骨骼发育不良。在此，我们表明造血干细胞（HSC）疗法有望治疗成骨不全症。在经致死辐射的oim/oim小鼠中使用单细胞 HSC 移植，我们证明了骨形态、力学和周转参数的显着改善。重要的是，我们强调，HSC 之所以能带来这些改善，是因为它们具有分化为成骨细胞/骨细胞、沉积正常胶原蛋白的独特特性，而这一特性迄今为止仅属于间充质干细胞/基质细胞。为了确认 HSC 可塑性，通过将来自两种特定转基因小鼠 VavR 的 HSC 移植到oim/oim来进行谱系追踪，其中所有造血细胞均为 GFP ⁺和 pOBCol2.3GFP，其中 GFP 仅在成骨细胞/骨细胞中表达。在这两种模型中，移植的oim/oim小鼠在骨骼中均表现出 GFP ⁺ HSC 衍生的成骨细胞/骨细胞。这些研究明确证实 HSC 分化为成骨细胞/骨细胞，HSC 移植可以为成骨不全症提供新的转化方法。