TRANSPLANTATION OF ALLOGENEIC MESENCHYMAL STEM CELLS

描述：(申请者摘要)人骨髓含有间充质 (间质)祖细胞(人间充质干细胞，hMSCs) 骨髓微环境中具有分化能力的外膜细胞 沿着各种间充质谱系，如成骨、成软骨、 成脂、成肌，可能是中枢神经系统内的星形胶质细胞。这些基质 祖细胞可以很容易地从骨髓中分离出来，并有选择地进行扩增 在体外转化为均匀的基质细胞群，而不会丢失它们的 多血统潜力。申请人最近证明，静脉注射 自体干细胞移植时将培养扩增的人骨髓间充质干细胞注入人体 细胞移植是可行的、安全的，可能与快速 造血植入。人血清白蛋白在体内的分布及生物学功能 培养扩增的人骨髓间充质干细胞目前还不是很清楚。收件人 异基因骨髓移植被证明可以再生他们的骨髓 基质主要来自寄主类型的细胞，以及来自申请人的初步数据 也表明受者hMSCs不是供者来源的。申请者假设 这是由于基质前体的数量很少或没有。 患者接受的造血干细胞移植。在此应用程序中，他 计划测试部分同种异体基质移植能否在 已稳定植入供体型造血细胞的患者 输注1~5×10(6)/kg培养扩增的供体hMSCs。在I期临床中 他将对接受异基因移植的遗传性疾病患者进行试验 干细胞移植，以纠正他们的疾病。他将利用 骨髓研究中患者和捐献者的遗传和表型差异 正常同种异体hMSCs的分布。此外，他还将确定是否有 是否从正常的hMSCs中获得任何临床益处。他的具体目标是 确定同种异体培养扩增的hMSCs能否安全地注入 曾接受过同种异体移植的患者 捐献者的造血细胞和同种异体hMSCs能否在 静脉输液后的宿主骨髓。这个项目将允许他 了解人骨髓间充质干细胞在人体内的移植生物学并扩大其治疗 发育成同种异体环境。

DESCRIPTION: (Applicant's Abstract) Human bone marrow contains mesenchymal (stromal) progenitors (human mesenchymal stem cells, hMSCs) that give rise to adventitial cells in the marrow micro environment capable of differentiating along the various mesenchymal lineages, such osteogenic, chondrogenic, adipogenic, myogenic, and perhaps to astroglial cells in CNS. These stromal progenitors can be readily isolated from bone marrow, and selectively expanded in vitro into a uniform population of stromal cells, without losing their multi-lineage potential. The applicant has recently shown that intravenous infusion of culture-expanded hMSC into humans at the time of autologous stem cell transplantation is feasible, safe, and may be associated with rapid hematopoietic engraftment. In vivo distribution and biologic function of culture-expanded hMSCs are not well understood at the present time. Recipients of allogeneic bone marrow transplantation were shown to regenerate their marrow stroma mainly from host-type cells, and preliminary data from the applicant also show that recipient hMSCs are not donor-origin. The applicant hypothesizes that this is due to low number or absence of stromal precursors within the hematopoietic stem cell graft that patients receive. In this application he plans to test whether partial allogeneic stromal engraftment can be achieved in patients already stably engrafted with donor type hematopoietic cells by infusion of 1-5 x 10(6)/kg culture expanded donor hMSCs. In a phase I clinical trial he will study patients with genetic disorders who underwent allogeneic stem cell transplantation for the correction of their disorder. He will utilize genetic and phenotypic differences between patients and donors to study marrow distribution of normal allogeneic hMSCs. In addition he will determine if there is any clinical benefit derived from normal hMSCs. His specific aims are to determine whether allogeneic culture expanded hMSCs can be safely infused into patients who had previously undergone allogeneic transplantation with same donors' hematopoietic cells and whether allogeneic hMSCs can be detected in the host marrow following their intravenous infusion. This project will allow him to learn transplantation biology of hMSCs in humans and expand its therapeutic development into allogeneic setting.