Stem Cells
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First published online December 1, 2005
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2005-0370v1
24/4/1054    most recent
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Submitted on August 4, 2005
Accepted on November 14, 2005

Original Article

Mesenchymal Stem Cells Spontaneously Express Neural Proteins in Culture, and Are Neurogenic After Transplantation

Jie Deng 1, Bryon E. Petersen 2, Dennis A. Steindler 3*, Marda L. Jorgensen 4, Eric D. Laywell 5

1 Anatomy & Cell Biology, Program in Stem Cell Biology & Regenerative Medicine, University of Florida, Gainesville, Florida
2 Pathology & Laboratory Medicine, Program in Stem Cell Biology & Regenerative Medicine, University of Florida, Gainesville, Florida
3 Neuroscience Department, McKnight Brain Institute, Program in Stem Cell Biology & Regenerative Medicine, University of Florida, Gainesville, Florida
4 Program in Stem Cell Biology & Regenerative Medicine, Universtiy of Florida, Gainesville, Florida
5 Anatomy & Cell Biology, McKnight Brain Institute, Program in Stem Cell Biology & Regenerative Medicine, University of Florida, Gainesville, Florida

* To whom correspondence should be addressed. E-mail: steindler{at}mbi.ufl.edu.


  Abstract

Reports of neural trans-differentiation of mesenchymal stem cells (MSCs) suggest the possibility that these cells may serve as source for stem cell-based regenerative medicine to treat neurological disorders. However, some recent studies controvert previous reports of MSC neurogenecity. In the current study, we evaluate the neural differentiation potential of mouse bone marrow-derived MSCs. Surprisingly, we found that MSCs spontaneously express certain neuronal phenotype markers in culture, in the absence of specialized induction reagents. A previously published neural induction protocol that elevates cytoplasmic cyclic AMP does not upregulate neuron-specific protein expression significantly in MSCs, but does significantly increase expression of the astrocyte-specific glial fibrillary acidic protein (GFAP). Finally, when grafted into the lateral ventricles of neonatal mouse brain, MSCs migrate extensively, and differentiate into olfactory bulb granule cells and periventricular astrocytes, without evidence of cell fusion. These results indicate that MSCs may be "primed" towards a neural fate by the constitutive expression of neuronal antigens, and seem to respond with an appropriate neural pattern of differentiation when exposed to the environment of the developing brain.




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