IN UTERO TRANSPLANTATION FOR LYSOSOMAL STORAGE DISEASE

出生后骨髓或外周血干细胞移植可以 有效地治疗许多涉及血细胞的遗传疾病， 由于其高成本、中等风险 以及缺乏合适的造血干细胞供体。 作为 重要的是，在某些疾病中，如溶酶体贮积症， 神经系统毒性在出生时发生， 移植 研究人员计划研究子宫内治疗 α-甘露糖苷中毒的症状除了移植造血干细胞 从成年猫到家猫胎儿的细胞，他们提出了两个新的 巨噬细胞前体细胞的子宫内移植 和子宫内基因转移（使用FeLV假型逆转录病毒载体 含有标记基因和/或MANB cDNA）。 调查人员还将 研究鼠ROSA 26中组织巨噬细胞植入的动力学 移植模型，以确定直接前体细胞， 脑中的小胶质细胞、肝中的枯否细胞和肺泡巨噬细胞 在肺部。 研究人员将定义细胞机制， 调解诉讼 在该鼠模型中的实验结果将 用于α-甘露糖苷沉积症的子宫内移植研究 在猫身上。 研究人员希望这些研究将提供 用于治疗溶酶体贮积症的替代方法。

Post-natal marrow or peripheral blood stem cell transplantation can effectively treat many genetic disorders which involve blood cells, but is not universally available because of its high cost, moderate risk, and the lack of suitable donors of hematopoietic stem cells. As importantly, in some diseases, such as the lysosomal storage disorders, neurologic toxicity occurs by birth, which is not reversible by transplantation. The investigators plan to study the in utero therapy of alpha-mannosidosis in cats. Besides transplanting hematopoietic stem cells from adult cats to domestic cat fetuses, they propose two novel approaches, the in utero transplantation of macrophage precursor cells and in utero gene transfer (with FeLV-pseudotyped, retroviral vectors containing marker genes and/or MANB cDNA). The investigators will also study the kinetics of tissue macrophage engraftment in a murine ROSA26 transplantation model, to identify the immediate precursor cell of microglia in brain, Kuppffer cells in liver, and alveolar macrophages in lung. The investigators will define the cellular mechanisms which mediate lodgment. The results of experiments in this murine model will be applied in the in utero transplantation studies of alpha-mannosidosis in cats. The investigators are hopeful that these studies will provide alternative approaches for the therapy of lysosomal storage disorders.