Methods, systems, and compositions for neuronal differentiation of multipotent stromal cells
Some embodiments of the invention comprise methods, systems, and compositions to selectively induce, whether in vitro or in vivo, the neuronal differentiation of multipotent stromal cells through the application of microRNAs, including but not limited to miRNA-124, miRNA-137 and/or miRNA-9* expression products of those miRNAs, and molecules and compositions containing functional elements of those miRNAs. Some embodiments of the invention also comprise the therapeutic administration and use of such induced cells to treat mammalian injuries and diseases, including but not limited to, nervous system injuries or diseases that may otherwise result in decreased cell or system function.
1. A method of trans-differentiating mammalian multipotent stromal cells into neuronal stem cells, the method comprising the steps of:
a) providing a population of mammalian multipotent stromal cells; and
b) expressing microRNA-137 in the population of mammalian multipotent stromal cells so as to generate a population of neuronal stem cells expressing nestin,
thereby trans-differentiating mammalian multipotent stromal cells into neuronal stem cells.
2. The method of claim 1 , wherein the mammal is a human.
3. The method of claim 1 , further comprising step (c) comprising analyzing a marker in said population of neuronal stem cells, wherein said marker comprises a neuronal morphology.
4. The method of claim 1 , wherein said mammalian multipotent stromal cells are derived from a tissue selected from the group consisting of adipose tissue, umbilical cord tissue, bone marrow tissue and placenta tissue.
5. The method of claim 1 , further comprising expressing in said mammalian multipotent stromal cells glial derived neurotrophic factor (GDNF).
6. The method of claim 1 , wherein said expressing comprises transfection, overexpression of exogenous miRNA or transduction of pre-miRNA.