Neural differentiation of human adipose-derived mesenchymal stem cells induced by glial cell conditioned media.

ABSTRACT

Adipose-derived mesenchymal stem cells (ASCs) may transdifferentiate into cells belonging to mesodermal, endodermal, and ectodermal lineages. The aim of this study was to verify whether a neural differentiation of ASCs could be induced by a conditioned medium (CM) obtained from cultures of olfactory ensheathing cells (OECs) or Schwann cells (SCs). ASCs were isolated from the stromal vascular fraction of adipose tissue and expanded for 2-3 passages. They were then cultured in OEC-CM or SC-CM for 24 hr or 7 days. At each stage, the cells were tested by immunocytochemistry and flow cytometer analysis to evaluate the expression of typical neural markers such as Nestin, PGP 9.5, MAP2, Synapsin I, and GFAP. Results show that both conditioned media induced similar positive effects, as all tested markers were overexpressed, especially at day 7. Overall, an evident trend toward neuronal or glial differentiation was not clearly detectable in many cases. Nevertheless, a higher tendency toward a neuronal phenotype was recognized for OEC-CM (considering MAP2 increases). On the other hand, SC-CM would be responsible for a more marked glial induction (considering GFAP increases). These findings confirm that environmental features can induce ASCs toward a neural differentiation, either as neuronal or glial elements. Rather than supplementing the culture medium by adding chemical agents, a "more physiological" condition was obtained here by means of soluble factors (cytokines/growth factors) likely released by glial cells. This culture strategy may provide valuable information in the development of cell-based therapeutic approaches for pathologies affecting the central/peripheral nervous system.