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Therapeutic Potential of Astrocyte Transplantation.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kuan, Wei-Li 
Osborne, Andrew 
Kotter, Mark RN 

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.

Description

Keywords

astrocyte, brain, injury, neurodegeneration, spinal cord, transplantation, Amyotrophic Lateral Sclerosis, Astrocytes, Humans, Huntington Disease, Neurodegenerative Diseases, Stroke

Journal Title

Cell Transplant

Conference Name

Journal ISSN

0963-6897
1555-3892

Volume Title

31

Publisher

SAGE Publications
Sponsorship
Medical Research Council (MR/S005528/1)
Addenbrooke's Charitable Trust (ACT) (Minute 38/19 B3)
Ferblanc Foundation (Unknown)
Rosetrees Trust (Seedcorn2020\100084)
Stoneygate Trust (Seedcorn2020\100084)
Addenbrooke's Charitable Trust (ACT) (900287, Minute 58/20A)
Addenbrooke's Charitable Trust (ACT) (900288, Minute 58/20B)
Department of Health (via National Institute for Health Research (NIHR)) (CS-2015-15-023)