Failure of transdifferentiation of adult hematopoietic stem cells into neurons

¹ Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund, Sweden
² Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
³ Department of Clinical Neuroscience, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden

^* To whom correspondence should be addressed. E-mail: Laurent.Roybon{at}med.lu.se.

	Abstract

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 (HSC), characterized by lineage marker depletion and expression of the cell surface markers Sca1 and c-Kit (LSK), can be stimulated to adopt a neuronal fate. When the HSC^LSK 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 post-mitotic. Electrophysiological recordings on neuron-like cells showed that these cells were incapable of generating action potentials. When the HSC^LSK were either 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 do not have the capacity to leave the hematopoietic lineage and differentiate into neurons.

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