Therapeutic Potential of Astrocyte Transplantation

Abstract

Cell transplantation is an attractive treatment strategy for a variety of brain disorders, as it promises to replenish lost functions and rejuvenate the brain. In particular, transplantation of astrocytes has come into light recently as a therapy for amyotrophic lateral sclerosis (ALS); moreover, grafting of astrocytes also showed positive results in models of other conditions ranging from neurodegenerative diseases of older age to traumatic injury and stroke. Despite clear differences in etiology, disorders such as ALS, Parkinson’s, Alzheimer’s, and Huntington’s diseases, as well as traumatic injury and stroke, converge on a number of underlying astrocytic abnormalities, which include inflammatory changes, mitochondrial damage, calcium signaling disturbance, hemichannel opening, and loss of glutamate transporters. In this review, we examine these convergent pathways leading to astrocyte dysfunction, and explore the existing evidence for a therapeutic potential of transplantation of healthy astrocytes in various models. Existing literature presents a wide variety of methods to generate astrocytes, or relevant precursor cells, for subsequent transplantation, while described outcomes of this type of treatment also differ between studies. We take technical differences between methodologies into account to understand the variability of therapeutic benefits, or lack thereof, at a deeper level. We conclude by discussing some key requirements of an astrocyte graft that would be most suitable for clinical applications.