Bone marrow transdifferentiation in brain after transplantation: a retrospective study
Bone marrow transdifferentiation in brain after transplantation: a retrospective study
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DOI：
10.1016/s0140-6736(04)16102-3
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发表时间：
2004-05-01
期刊：
影响因子：
168.9
通讯作者：
Scott, EW
中科院分区：
文献类型：
--
作者：
Cogle, CR;Yachnis, AT;Scott, EW
背景成体造血干细胞的终末器官修复受到了广泛关注，研究人员对这些细胞的可塑性提出了质疑。一些动物和短期人类骨髓移植的研究表明，骨髓可以修复大脑。我们寻找临床相关的骨髓源性恢复性神经发生的证据：长期的，多系的，神经植入，是不是结果的cell-fusion events.Methods我们检查了尸检脑标本从三个性别不匹配的女性骨髓移植患者，女性对照，和男性对照。我们做了免疫组化，荧光原位杂交，组织分析，寻找多系，供体来源的neurogenesis. Findings海马细胞含有Y染色体移植后6年在所有三名患者。跨性别神经元占所有神经元的1%;没有证据表明融合事件，因为只有一个X染色体存在。此外，变性的星形胶质细胞和小胶质细胞占所有胶质细胞的1 - 2%。解释出生后的人类神经发生，人类造血细胞可以在长期环境中转分化为神经元，星形胶质细胞和小胶质细胞而不融合。可移植的人类造血细胞可以作为长期再生神经的治疗来源。
Background End-organ repair by adult haemopoietic stem cells is under great scrutiny with investigators challenging the notion of these cells' plasticity. Some investigations of animals and short-term human bone marrow transplants suggest that bone marrow can repair brain. We looked for evidence of clinically relevant marrow-derived restorative neurogenesis: long-term, multilineage, neural engraftment that is not the result of cell-fusion events.Methods We examined autopsy brain specimens from three sex-mismatched female bone-marrow-transplantation patients, a female control, and a male control. We did immunohistochemistry, fluorescence in-situ hybridisation, and tissue analysis to look for multilineage, donor-derived neurogenesis.Findings Hippocampal cells containing a Y chromosome were present up to 6 years post-transplant in all three patients. Transgender neurons accounted for 1% of all neurons; there was no evidence of fusion events since only one X chromosome was present. Moreover, transgender astrocytes and microglia made up 1-2% of all glial cells.Interpretation Postnatal human neuropoiesis happens, and human haemopoietic cells can transdifferentiate into neurons, astrocytes, and microglia in a long-term setting without fusing. Transplantable human haemopoietic cells could serve as a therapeutic source for long-term regenerative neuropoiesis.