Crain Barbara J, Tran Simon D, Mezey Eva
Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
J Neurol Sci. 2005 Jun 15;233(1-2):121-3. doi: 10.1016/j.jns.2005.03.017. Epub 2005 Apr 21.
Multiple studies have reported that adult cells of bone marrow origin can differentiate into muscle, skin, liver, lung, epithelial cells, and neurons. To determine whether such cells might produce neurons and other cells in the human brain, we examined paraffin sections from female patients who had received bone marrow transplants from male donors. Y-chromosomes were labeled using autoradiography and fluorescent in situ hybridization. Neurons and astrocytes were identified histologically and immunohistochemically in neocortex, hippocampus, striatum, and cerebellum. However, most labeled cells in both gray and white matter appeared to be glia. Others have suggested that such Y-labeling represents fusion between host and donor cells, rather than true transdifferentiation. The possibilities of fusion and microchimerism were therefore examined using buccal epithelial cells as a model system. The female patients in this study had received either bone marrow or stem cell (CD34+ enriched) transplants from their brothers. Double labeling for X- and Y-chromosomes showed that Y-labeled buccal cells could not be explained by fusion. Genotyping studies of one patient, her brother, and her son ruled out the possibility of microchimerism. Whether, and under what circumstances, some form of bone marrow transplantation might provide adequate number of cells capable of replacing lost brain cells or enhancing their function will require additional studies.
多项研究报告称，骨髓来源的成体细胞可分化为肌肉、皮肤、肝脏、肺、上皮细胞和神经元。为了确定此类细胞是否可能在人类大脑中产生神经元和其他细胞，我们检查了接受男性供体骨髓移植的女性患者的石蜡切片。使用放射自显影和荧光原位杂交对Y染色体进行标记。在新皮质、海马体、纹状体和小脑中通过组织学和免疫组织化学方法鉴定神经元和星形胶质细胞。然而，灰质和白质中大多数标记细胞似乎是神经胶质细胞。其他人认为，这种Y标记代表宿主细胞与供体细胞之间的融合，而非真正的转分化。因此，以颊上皮细胞作为模型系统研究了融合和微嵌合体的可能性。本研究中的女性患者接受了来自其兄弟的骨髓或干细胞（富集CD34+）移植。对X和Y染色体进行双重标记显示，Y标记的颊细胞无法用融合来解释。对一名患者、她的兄弟和她的儿子进行的基因分型研究排除了微嵌合体的可能性。某种形式的骨髓移植是否以及在何种情况下能够提供足够数量的细胞来替代丢失的脑细胞或增强其功能，这需要进一步研究。
