Transplanted human bone marrow cells generate new brain cells

被引:55
作者
Crain, BJ
Tran, SD
Mezey, E
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[2] Natl Inst Dental & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA
[3] NINDS, Basic Neurosci Program, NIH, Bethesda, MD USA
关键词
human; bone marrow transplantation; neurons; glia; buccal epithelium; cell fusion; transdifferentiation;
D O I
10.1016/j.jns.2005.03.017
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:121 / 123
页数:3
相关论文
共 23 条
[1]   Cell differentiation - Hepatocytes from nonhepatic adult stem cells [J].
Alison, MR ;
Poulsom, R ;
Jeffery, R ;
Dhillon, AP ;
Quaglia, A ;
Jacob, J ;
Novelli, M ;
Prentice, G ;
Williamson, J ;
Wright, NA .
NATURE, 2000, 406 (6793) :257-257
[2]   Can stem cells cross lineage boundaries? [J].
Anderson, DJ ;
Gage, FH ;
Weissman, IL .
NATURE MEDICINE, 2001, 7 (04) :393-395
[3]   Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice [J].
Bittner, RE ;
Schöfer, C ;
Weipoltshammer, K ;
Ivanova, S ;
Streubel, B ;
Hauser, E ;
Freilinger, M ;
Höger, H ;
Elbe-Bürger, A ;
Wachtler, F .
ANATOMY AND EMBRYOLOGY, 1999, 199 (05) :391-396
[4]   From marrow to brain: Expression of neuronal phenotypes in adult mice [J].
Brazelton, TR ;
Rossi, FMV ;
Keshet, GI ;
Blau, HM .
SCIENCE, 2000, 290 (5497) :1775-1779
[5]   Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice [J].
Eglitis, MA ;
Mezey, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :4080-4085
[6]   Muscle regeneration by bone marrow derived myogenic progenitors [J].
Ferrari, G ;
Cusella-De Angelis, G ;
Coletta, M ;
Paolucci, E ;
Stornaiuolo, A ;
Cossu, G ;
Mavilio, F .
SCIENCE, 1998, 279 (5356) :1528-1530
[7]  
Gussoni E, 1999, NATURE, V401, P390, DOI 10.1038/43922
[8]   PERIVASCULAR MICROGLIAL CELLS OF THE CNS ARE BONE-MARROW DERIVED AND PRESENT ANTIGEN INVIVO [J].
HICKEY, WF ;
KIMURA, H .
SCIENCE, 1988, 239 (4837) :290-292
[9]   Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. [J].
Korbling, M ;
Katz, RL ;
Khanna, A ;
Ruifrok, AC ;
Rondon, G ;
Albitar, M ;
Champlin, RE ;
Estrov, Z .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (10) :738-746
[10]   Purified hematopoietic stem cells can differentiate into hepatocytes in vivo [J].
Lagasse, E ;
Connors, H ;
Al-Dhalimy, M ;
Reitsma, M ;
Dohse, M ;
Osborne, L ;
Wang, X ;
Finegold, M ;
Weissman, IL ;
Grompe, M .
NATURE MEDICINE, 2000, 6 (11) :1229-1234