GEN News Highlights: Nov 3, 2011

Dedifferentiating Neuronal Progenitors to Stem-Like State Increases Survival In Vivo and Boosts Therapeutic Effects
Chinese University of Hong Kong

Prompting expanded mesenchymal stem cells (MSCs) to undergo neuronal differentiation and then triggering them to dedifferentiate back to a more stem-like state results in a population of cells that exhibits enhanced survival when transplanted in vivo, and a greater ability to redifferentiate back into neuronal cells, investigators claim.

A team led by researchers at the Chinese University of Hong Kong was interested to see whether MSC-derived neuronal progenitor cells that were dedifferentiated (de-MSCs) would have different properties to the MSCs from which they were originally derived. Their findings showed that the de-MSCs displayed multipotent gene expression profiles similar to those of their unmanipulated MSC counterparts, but also upregulated the expression of genes required for neuronal differentiation and survival.

When MSCs and de-MSCs were then transplanted into a rat model of brain damage, the de-MSCs demonstrated a significant survival advantage, and led to comparatively greater levels of functional improvement in treated animals. The University’s Hsiao Chang Chan, Ph.D., and colleagues, suggest their findings could translate into more effective stem-cell based regenerative therapies. “It may provide a novel and clinical practical method to overcome low cell survival in cell-based therapy,” Dr. Chan states. “We are currently exploring other beneficial properties of the reprogrammed MSCs for other therapeutic applications.”

The team reports its findings in Stem Cell in a paper titled “Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential.”

Research has demonstrated that bone marrow stromal stem cells, also known as mesenchymal stem cells, have the capacity to differentiate into a wide range of cell types outside the mesodermal lineage, including neuron-like cells, the researchers report. Unfortunately, while transplantation studies using MSC-derived cells in animal models of diseases including Parkinson disease, stroke, cerebral ischemia, and spinal cord injury have shown beneficial effects, most have reported low levels of cell survival and neuronal differentiation in vivo.