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

Abstract

IntroductionUmbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are self-renewing multipotent progenitors with the potential to differentiate into multiple lineages of mesoderm, in addition to generating ectodermal and endodermal lineages by crossing the germline barrier. In the present study we have investigated the ability of UCB-MSCs to generate neurons, since we were able to observe varying degrees 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 stepwise protocol. Our hypothesis was therefore that the human UCB-MSCs would contain multiple types of progenitors with varying neurogenic potential and that the ratio of the progenitors with high and low neurogenic potentials varies in different batches of UCB.MethodsIn total we collected 45 UCB samples, nine of which generated MSCs that were further expanded and characterized using immunofluorescence, fluorescence-activated cell sorting and RT-PCR analysis. The neuronal differentiation potential of the UCB-MSCs was analyzed with exposure to combination of growth factors.ResultsWe could identify two different populations of progenitors within the UCB-MSCs. One population represented progenitors 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, requires extensive exposure to a combination of growth factors to transdifferentiate into neurons. Interesting to note was that both of these cell populations were positive for CD29 and CD105, indicating their MSC lineage, but showed prominent difference in their neurogenic potential.ConclusionOur results suggest that the expanded UCB-derived MSCs harbor a small unique population of cells that 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; the ratio of these pluripotent marker expressing cells in a batch determines the innate neurogenic potential.

Human Antigen R Binding and Regulation of SOX2 mRNA in Human Mesenchymal Stem Cells

“…When the total SOX2 messenger was assessed, we observed an upregulation induced by both MTX and the reprogramming drug BIX01294, whereas the prodifferentiating agent PMA caused a downregulation, as expected ( Fig. 3B) (Divya et al, 2012). Moreover, the ability of MTX in inducing SOX2 mRNA upregulation was also assessed in non-MSCs (adult neural stem cells), with a similar outcome (Supplemental Fig.…”

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

“…Human umbilical cord blood-derived MSCs were generated according to previously described methods (13,41). Details can be found in the Supplementary Materials and Methods section.…”

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

“…The treatment aimed at activating proliferation, differentiation and migration of endogenous VCCs provides a therapeutic option to enhance natural neuroregenerative mechanisms. A source of mesenchymal stem cells like VCCs is capable of differentiating into mesenchymal and potentially even neuronal lineages [52]. In ALS models, the motor neuron degeneration triggers endogenous NPCs niches in the CNS to proliferate, migrate, and promote neurogenesis in the spinal cord as a natural response to disease [9,53]; however, the limited number of proliferative, migrated endogenous NPCs is likely insufficient to combat the progressive motor neuron degeneration associated with ALS.…”