Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E⁺ (CD73)⁺ ENG^- (CD105)^- LY6A⁺ (SCA1)⁺ BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation.

中文翻译：

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长期植入原代骨髓基质细胞可修复小生境损伤并改善造血干细胞移植。

造血干细胞（HSC）移植代表了多种血液系统疾病的治疗方法。然而，先天性免疫和适应性免疫的重建延迟通常会导致致命的并发症。HSC的维持和沿袭分化受基质小生境的支持，我们现在发现，骨髓基质细胞（BMSC）受到有效HSC移植所需的预处理辐射的严重和永久性破坏。使用小鼠模型，我们表明基质功能不全限制了供体来源的HSC和B淋巴细胞生成的数量。伯，但不是培养，骨髓干细胞的内骨移植定量重新构成在体内基质的功能，其由多能介导NT5E ⁺（CD73）⁺ ENG ^-（CD105）^-LY6A ⁺（SCA1）⁺ BMSC亚群。BMSC共移植使功能性，供体来源的HSC数量增加了一倍，并显着降低了与HSC移植相关的临床相关副作用，包括中性粒细胞减少和体液免疫缺陷。这些数据表明基质恢复的潜力，以改善HSC移植。