Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells

被引:356
作者
Hermann, A
Gastl, R
Liebau, S
Popa, MO
Fiedler, J
Boehm, BO
Maisel, M
Lerche, H
Schwarz, J
Brenner, R
Storch, A
机构
[1] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany
[2] Univ Ulm, Dept Appl Physiol, D-89081 Ulm, Germany
[3] Univ Ulm, Div Biochem Joint & Connect Tissue Dis, Dept Orthopaed, D-89081 Ulm, Germany
[4] Univ Ulm, Div Endocrinol, Dept Internal Med, D-89081 Ulm, Germany
[5] Univ Leipzig, Dept Neurol, D-04103 Leipzig, Germany
[6] CALTECH, Div Biol, Pasadena, CA 91125 USA
关键词
mesodermal stromal cells; neural stem cells; transdifferentiation; neural differentiation; human stem cells;
D O I
10.1242/jcs.01307
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Clonogenic neural stem cells (NSCs) are self-renewing cells that maintain the capacity to differentiate into brain-specific cell types, and may also replace or repair diseased brain tissue. NSCs can be directly isolated from fetal or adult nervous tissue, or derived from embryonic stem cells. Here, we describe the efficient conversion of human adult bone marrow stromal cells (hMSC) into a neural stem cell-like population (hmNSC, for human marrow-derived NSC-like cells). These cells grow in neurosphere-like structures, express high levels of early neuroectodermal markers, such as the proneural genes NeuroD1, Neurog2, MSl1 as well as otx1 and nestin, but lose the characteristics of mesodermal stromal cells. In the presence of selected growth factors, hmNSCs can be differentiated into the three main neural phenotypes: astroglia, oligodendroglia and neurons. Clonal analysis demonstrates that individual hmNSCs are multipotent and retain the capacity to generate both glia and neurons. Our cell culture system provides a powerful tool for investigating the molecular mechanisms of neural differentiation in adult human NSCs. hmNSCs may therefore ultimately help to treat acute and chronic neurodegenerative diseases.
引用
收藏
页码:4411 / 4422
页数:12
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