What is it about?

The biggest hurdle for having enough stem cells for gene therapy is to be able to expand the initial stem cell population without inducing terminal differentiation or altering the genome. One of the unique biomarkers of a stem cell is its ability to divide either symmetrically to have both daughters maintaining "stemness" properties, or to divide aysmetrically to have one daughter maintaining stemness, while the other daughter having the ability to terminally differentiate. Another critical biomarkers of stem cells is its expression of the Oct4A gene, while suppressing its connexin genes, which are needed for growth control, differentiation, apoptosis and senescence. Our team has found that , among the several ways to prevent stem cells having functional gap junctions, one strategy was to inhibit gap junction function in any stem cell, that started to express its connexin gene, its protein anf its function, was to treat these stem cell populations with a non-genotoxic chemical, DDT.

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Why is it important?

By preventing asymmetrical cell division, only those stem cells that divided symmetrically survive., allowing an unending population of the stem cells to expand. That means there will always be a supply of these stem cells for sufficient cells that will be needed for stem cell therapy or for repeated therapy. When those stem cells populations are ready for the desired differentiation, the DDT is removed and any specific inducer of the required differentiation of that organ-specific adult stem cell lineage can be applied.

Perspectives

There are two major implications of our findings. First, one can use a non-genetically-altered stem cells by using an adult human adult organ-specific stem cell for gene therapy. The second is, this use of a technique to prevent the expression of functional gap junctions , while naturally occurs during the expansion of stem cells, will allow continous expansion of symmetrically-dividing cells.

Prof essor James E Trosko
Michigan State University

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This page is a summary of: Inhibition of Gap Junctional Intercellular Communication Upregulates Pluripotency Gene Expression in Endogenous Pluripotent Muse Cells, Cells, August 2022, MDPI AG,
DOI: 10.3390/cells11172701.
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