UCLA researchers in the Department of Neurology and the Department of Molecular, Cell & Developmental Biology have developed novel therapies for cerebral ischemic injuries, including white matter stroke, using glial-enriched progenitor cells.
During the normal human aging process, the white matter regions of the brain suffer progressive damage related to both overt and clinically silent ischemia. The degree of white matter injuries closely correlates with abnormalities in cognition, balance, and gait, additionally carrying an increased risk of death. Progressive accumulation of cerebral white matter lesions is indicative of white matter stroke (WMS), which results in dementia over time or worsens symptoms when combined with Alzheimer’s disease. Currently, there is no therapy available for WMS.
The neural elements damaged in WMS include oligodendrocytes, oligodendrocyte progenitor cells (OPCs), astrocytes and axons. Astrocytes promote OPC survival and differentiation into the myelinating oligodendrocytes. Astrocyte- or glial-restricted progenitor cells have been shown to mitigate to injuries and promote stabilization of injured axons and growth of new connections in spinal cord injury transplant therapies. However, routine production of astrocyte- or glial-restricted progenitor cells from fetal-derived neural precursors is not possible for use in treatment in WMS because of the large volumes of cells that would be required for human therapy. In addition, production of glial-restricted or glial-enriched progenitors from embryonic stem cells or induced pluripotent stem cells is time-consuming and extremely inefficient.
Therefore, there is a need to develop novel therapies for cerebral ischemic injuries, including WMS. Moreover, there is a need for production of glial-enriched progenitor cells for use in cellular treatment for conditions requiring myelin repair and/or remyelination, such as WMS.
Researchers at UCLA have developed novel therapies for treatment of cerebral ischemic injuries, including white matter stroke, that involve the administration of induced pluripotent glial-enriched progenitor cells. This new approach is able to repair neuronal networks disrupted by ischemic stroke. Experiments have shown increased myelination within the damaged white matter and reduced measures of reactive astrocytosis and inflammation post treatment.
Provides a renewable and scalable source of glial-enriched progenitors for therapeutics and research
Successfully tested in vivo in mouse models.
|United States Of America||Published Application||20180271911||09/27/2018||2016-170|
|European Patent Office||Published Application||3355898||08/08/2018||2016-170|
|Japan||Published Application||WO 2017/058819A||04/06/2017||2016-170|
Ischemic injury, white matter stroke, therapeutic, stem cell, pluripotent, glial-enriched progenitor cell, myelination, research tool