异基因造血干细胞移植已经成为部分重型再障患者的一线治疗方案。促进造血干细胞植入及造血重建是提高干细胞移植成功率的关键。再障患者T细胞功能紊乱，间充质干细胞成骨及成脂发育不平衡，其基质细胞体外支持造血功能差。在前期研究中，我们发现无论何种原因引起的骨龛功能缺陷均可致其内造血干细胞造血重建能力降低。因此移植后骨龛功能缺陷可能是供者干细胞植入失败及造血重建不佳的重要原因。本课题拟利用临床标本找到重再患者T细胞表达的影响MSC成骨成脂的关键Wnt蛋白，阐明其中T细胞辅助增强PTH作用的机制，研究重再患者移植后骨龛与干细胞植入及造血重建的关系。创新点是阐明重再患者T细胞缺陷所致MSC成骨成脂不平衡的机制，证明成骨细胞龛功能缺陷是重再患者造血干细胞植入失败的重要原因。

Allogeneic hematopoietic stem cell transplantation has become the first-line treatment for some patients with severe aplastic anemia. Promotion of hematopoietic stem cell implantation and reconstitution is the key point to improve the success rate of transplantation. Abnormal T cell function occurs together with imbalance between adipogenesis and osteogenesis of mesenchyma stromal cell in acquired anemia. Moreover, the stromal cells support hematopoietic reconstitution poorly in vitro. Our previous research indicated that the defects of bone niche function could reduce the ability of hematopoietic reconstruction. Accordingly, bone niche dysfunction may be an important reason for stem cell implantation failure and poor hematopoietic reconstitution after transplantation. This research will involve several aspects concerning:the key Wnt protein expressed by T cell; the role of T cell in PTH application and the relationship between bone niche and stem cell implantation and reconstitution by using clinical samples; The points of the study are to elucidate the role of T cell in imbalance between adipogenesis and osteogenesis of mesenchyma stromal cell, to prove that bone niche dysfunction is an important cause of stem cell implantation failure.

异基因造血干细胞移植已经成为部分重型再障患者的一线治疗方案。促进造血干细胞植入及造血重建是提高干细胞移植成功率的关键。再障患者T细胞功能紊乱，间充质干细胞成骨及成脂发育不平衡，其基质细胞体外支持造血功能差。在前期研究中，我们发现无论何种原因引起的骨龛功能缺陷均可致其内造血干细胞造血重建能力降低。因此移植后骨间充质干细胞及成骨细胞龛功能缺陷可能是供者干细胞植入失败及造血重建不佳的重要原因。我们的研究阐明，1)与正常供者相比，再障患者血清PTH水平无明显差异；且初诊再障患者骨髓T细胞PTH受体PTH1R基因表达水平亦无明显差异，提示再障患者骨髓间充质干细胞成骨分化受抑并非因PTH水平过低或T细胞PTH受体表达降低所致。2)通过对3例植入后造血重建不良的再障患者骨髓间充质干细胞的研究发现移植后骨髓间充质干细胞虽然在免疫表型上与植入及造血重建良好者无明显差异，但是与后者相比，其间充质干细胞增值不佳，易凋亡且成骨分化受抑，提示对于造血重建不良的再障患者其成骨细胞龛可能是决定造血干细胞是否顺利植入及造血重建的关键因素。