Supercharged Mesenchymal Stem Cells

Kobe, Japan -

The ability to expand stem cells in culture without their differentiation is one of the features that makes embryonic stem cells attract a lot of attention. For example, in one of the classical WARF patents, the claim is made regarding ability of the embryonic stem cell to proliferate in an undifferentiated state for at least one year. Unfortunately there are concerns about embryonic stem cells in terms of ability to control their differentiation, the fears of immune rejection, as well as potential for causing teratomas. For this reason there has been a lot of work performed in terms of clinically developing adult stem cell types.

One such stem cell type, the mesenchymal stem cell, is attractive since it appears to be capable of acting as a universal donor cell and is capable of differentiating into numerous types of tissue including cardiac cells, neurons, hepatocytes and bone. Mesenchymal stem cells derived from the bone marrow are currently in clinical trials and have demonstrated potent effects in heart failure when administered intravenously. Unfortunately, in many situations bone marrow derived mesenchymal stem cells can only be expanded a certain number of times before senescence occurs, or even before senescence the cells loose differentiation potential.

A couple of months ago it was reported that the transfection of adult somatic cells with sox-2, c-myc, oct-3/4 and klf-4 was able to induce retrodifferentiation into embryonic stem cells, so an interesting question is whether these type of transfections can be used to "rejuvenate" adult stem cells. In a recent paper (Go et al. Forced expression of Sox2 or Nanog in human bone marrow derived mesenchymal stem cells maintains their expansion and differentiation capabilities. Exp Cell Res. 2007 Dec 4) this is exactly what was attempted.

The scientists transfected human bone marrow derived mesenchymal stem cells with either the Sox-2 gene or the NANOG gene, both genes associated with "dedifferentiation". It was observed that transfected cells had a more "immature" morphology as detected by smaller, rounder, shape. Additionally, the transfected cells possessed a higher ability to retain osteogenic capacity after long-term expansion as compared to the non-transfected cells.

These data support investigation into other agents that may be capable of expanding stem cells through pharmacological means, which would be easier and safer than full-blown transfection. Here at StemCellPatents.com we have already discussed this possibility by using histone deacetylase inhibitors such as valproic acid as well as other agents. The possibility of pharmaceutical manipulation of endogenous stem cells should not be seen as something far in the future. Currently there is a publication demonstrating inhibition of
post infarct remodelling by administration of valproic acid in a rat model. Additionally, companies such as Stem Cell Therapeutics from Calgary Canada are already in Phase II of clinical trials expanding neural stem cells after stroke through administration of erythropoietin and human chorionic gonadotropin.