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First published online 10 August 2004
doi: 10.1242/jcs.01307

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

Andreas Hermann^1,*, Regina Gastl^1,*, Stefan Liebau¹, M. Oana Popa², Jörg Fiedler³, Bernhard O. Boehm⁴, Martina Maisel¹, Holger Lerche^1,2, Johannes Schwarz^5,6, Rolf Brenner³ and Alexander Storch^1,

¹ Department of Neurology, University of Ulm, Helmholtzstr. 8/1, 89081 Ulm, Germany
² Department of Applied Physiology, University of Ulm, Helmholtzstr. 8/1, 89081 Ulm, Germany
³ Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedics, University of Ulm, Helmholtzstr. 8/1, 89081 Ulm, Germany
⁴ Division of Endocrinology, Department of Internal Medicine, University of Ulm, Helmholtzstr. 8/1, 89081 Ulm, Germany
⁵ Department of Neurology, University of Leipzig, Liebigstr. 22a, 04103 Leipzig, Germany
⁶ Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA

Author for correspondence (e-mail: alexander.storch{at}neuro.med.tu-dresden.de)

Accepted 5 May 2004

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.

Key words: Mesodermal stromal cells, Neural stem cells, Transdifferentiation, Neural differentiation, Human stem cells

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