Cell Therapy to Enhance the Repair Response of the Brain

In today's research materials, researchers present an approach to cell therapy involving the delivery of progenitor cells that are biased to differentiate into astrocytes. Further, the astrocytes so produced are primed to undertake repair activities in the brain. This sort of regenerative approach is in principle applicable to a range of issues, from structural damage to the brain, such as that resulting from injury or stroke, to more subtle issues such as demyelination and the progressively worsening consequences of age-related neurodegeneration.

The advantage of progenitor cells and stem cells, particularly the pluripotent cells that are now easily manufactured by any competent lab, is that they can take on the characteristics of many different cell types. This is also the disadvantage when one wants a very particular type of cell and class of cell behavior. In principle, the robust methods of production of pluripotent cells make it more cost effective to turn out any cell type needed. In practice, the challenge lies in finding the recipe of signals and environment to ensure that the resulting differentiated cells perform in the desired way. This recipe is different for every scenario, and this is one of the reasons why progress towards cell based regenerative therapies is slower than we would all like it to be.

Stem cell therapy promotes recovery from stroke and dementia in mice

The two most common causes of dementia are Alzheimer's disease and white matter strokes - small strokes that accumulate in the connecting areas of the brain. Currently, there are no therapies capable of stopping the progression of white matter strokes or enhancing the brain's limited ability to repair itself after they occur. Now a new study identifies a cell therapy that can stop the progressive damage caused by the disease and stimulate the brain's own repair processes.

The cells used in the therapy are a specialized type of glial cells, which are cells that surround and support neurons in the central nervous system. Researchers evaluated the effects of their glial cell therapy by injecting it into the brains of mice with brain damage similar to that seen in humans in the early to middle stages of dementia. Upon injection, the cells traveled to damaged areas of the brain and secreted growth factors that stimulated the brain's stem cells to launch a repair response. Activating that repair process not only limited the progression of damage, but it also enhanced the formation of new neural connections and increased the production of myelin - a fatty substance that covers and protects the connections.

Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents

Astrocytes, axons, and myelin are subjected to major damage during subcortical white matter stroke (WMS), a debilitating disorder leading to cognitive and motor impairments. Previous studies have shown that immature astrocyte transplantation could promote remyelination in rodent models. Now, a team has used a model of WMS in mice to demonstrate that transplantation of glial enriched progenitor cells differentiated from human-induced pluripotent stem cells (hiPSC-GEPs) shortly after stroke matured into a mature astrocyte phenotype and had therapeutic effect on axonal damage, demyelination, and cognitive impairments more effectively than hiPSC-derived neuronal precursor cells. The results suggest that astrocyte precursors have therapeutic potential in stroke.