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TISSUE-SPECIFIC STEM CELLS

Failure of Transdifferentiation of Adult Hematopoietic Stem Cells into Neurons

^a Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund, Sweden;
^b Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden;
^c Department of Clinical Neuroscience, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden

Key Words. Adult hematopoietic stem cells • Fluorescence-activated cell sorting • Plasticity • Neural stem cells • Microglia • Macrophage • Transdifferentiation

Correspondence: Laurent Roybon, M.Sc., Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden. Telephone: +46 46 2220526; Fax: +46 73 0564677; e-mail: Laurent.Roybon{at}med.lu.se

Received November 7, 2005; accepted for publication March 14, 2006.

Previous studies of bone marrow-derived stem cell transdifferentiation into neurons have not involved purified cell populations and determined their exact phenotype prior to differentiation. The present study investigates whether highly purified mouse adult hematopoietic stem cells (HSCs), characterized by lineage marker depletion and expression of the cell surface markers Sca1 and c-Kit (Lin^– Sca1⁺ c-Kit⁺ [LSK]), can be stimulated to adopt a neuronal fate. When the HSC^LSK cells were cultured in vitro in neuronal differentiation medium supplemented with retinoic acid, 50% of the cells expressed the neural progenitor marker nestin and no cells had become postmitotic. Electrophysiological recordings on neuron-like cells showed that these cells were incapable of generating action potentials. When the HSC^LSK cells either were grown in vitro together with neural precursor cells or were transplanted into the striatum or cerebellum of wild-type mouse, they either differentiated into Iba1-immunopositive macrophage/microglia or died. In conclusion, we demonstrate that adult HSC^LSK cells do not have the capacity to leave the hematopoietic lineage and differentiate into neurons.

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