Umbilical cord blood-derived mesenchymal stem cells consist of a unique population of progenitors co-expressing mesenchymal stem cell and neuronal markers capable of instantaneous neuronal differentiation

INTRODUCTION:Umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) are self-renewing multi-potent progenitors having the potential to differentiate into multiple lineages of mesoderm, in addition to generating ectodermal and endodermal lineages by crossing the germ-line barrier. In the present study we have investigated the ability of UCB-MSCs to generate neurons since, we were able to observe varying degree of neuronal differentiation from a few batches of UCB-MSCs with very simple neuronal induction protocols whereas, other batches required extensive exposure to combination of growth factors in a step wise protocol. Therefore, our hypothesis was that the hUCB-MSCs would contain multiple types of progenitors with varying neurogenic potential and the ratio of the progenitors with high and low neurogenic potentials varies in different batches of UCB.METHODS:In total we have collected 45 UCB samples out of which 9 generated MSCs which were further expanded and characterized using immunofluorescence, fluorescence-activated cell sorting (FACS) and RT-PCR analysis. The neuronal differentiation potential of the UCB-MSCs was analyzed with exposure to combination of growth factors.RESULTS:We could identify two different populations of progenitors within the UCB-MSCs. One with innate neurogenic potential that initially express pluripotent stem cell markers such as Oct4, Nanog, Sox2, ABCG2 and neuro-ectodermal marker nestin and are capable of expanding and differentiating into neurons with exposure to simple neuronal induction conditions. The remaining population of cells, typically expressing MSC markers require extensive exposure to combination of growth factors to trans-differentiate them into neurons. It was also interesting to note that both these population of cells were positive for CD29 and CD105, indicating their MSC lineage but showed prominent difference in their neurogenic potential.CONCLUSIONS:Our results suggest that the expanded UCB-derived MSCs harbour a small unique population of cells which express pluripotent stem cell markers along with MSC markers and possess an inherent neurogenic potential. These pluripotent progenitors later generate cells expressing neural progenitor markers and are responsible for the instantaneous neuronal differentiation and it is the ratio of these pluripotent marker expressing cells in a batch that determine the innate neurogenic potential.