Science：改进骨髓移植预处理的新线索
用小鼠进行的新研究提出一个改进骨髓移植效率的方法，从而使捐献的干细胞能更多地成活并且开始为身体供血作贡献。研究人员说，在移植前用一个抗体将宿主现有干细胞耗尽的方法产生的副作用，也许比现在用的准备身体接受移植的常规预处理的方法要小。虽然骨髓移植的成功部分地取决于宿主的免疫系统接受还是排斥新细胞，但有证据(比如移植在有严重免疫缺陷患者的身上失败)表明还有其他障碍存在。Agnieszka Czechowicz和同事现在揭示，在一个小鼠模型中，宿主现有的造血干细胞阻碍捐献干细胞的植入。他们用名为ACK2的抗体做试验，该抗体识别和阻碍一个被称为c-kit的酶，该酶是造血干细胞一个重要的调节因子。将这个抗体注入小鼠体内，耗尽了现有的干细胞，为移植细胞的植入清除了障碍。虽然这一方法是否能用于人类还需要进一步研究，但是文章作者提出，用类似ACK2的抗体也许是“一个取代常规预处理方法的有吸引力的选择，现有方法有很大的健康风险”。（科学时报）
原始出处:
Science 23 November 2007:
Vol. 318. no. 5854, pp. 1296 - 1299
DOI: 10.1126/science.1149726
Efficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches
Agnieszka Czechowicz, Daniel Kraft, Irving L. Weissman,*
Deepta Bhattacharya
Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these mice with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation.
Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
These authors contributed equally to this work.
* To whom correspondence should be addressed. E-mail: irv@stanford.edu
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