Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the selective loss of both spinal and upper motor neurons. One strategy in treating ALS is to use stem cells to replace lost spinal motor neurons. However, transplanted stem cell-derived motor neurons may not survive when exposed to the harsh microenvironment in the spinal cord of ALS. In particular, dysfunctional astrocytes and overactivated microglia in ALS may limit the survival of motor neurons generated from cell replacement therapy. On the other hand, stem cells may provide large quantities of motor neurons that can be used for studying glia-mediated toxic mechanisms and potential therapies in ALS. Here we will review methods and molecular factors for directed differentiation of stem cells into spinal motor neurons, the potential uses of these models for dissecting the mechanisms underlying glia-induced motor neuron degeneration and screening for new therapeutics aimed at protecting motor neurons in ALS, as well as discuss challenges facing the development of motor neuron replacement-based cell therapies for recovery in ALS.
Keywords: Amyotrophic lateral sclerosis, stem cell, motor neuron, microglia, astrocyte, transplantation
Current Stem Cell Research & Therapy
Title: Stem Cell-Derived Motor Neurons: Applications and Challenges in Amyotrophic Lateral Sclerosis
Volume: 4 Issue: 3
Author(s): Jason R. Thonhoff, Luis Ojeda and Ping Wu
Affiliation:
Keywords: Amyotrophic lateral sclerosis, stem cell, motor neuron, microglia, astrocyte, transplantation
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the selective loss of both spinal and upper motor neurons. One strategy in treating ALS is to use stem cells to replace lost spinal motor neurons. However, transplanted stem cell-derived motor neurons may not survive when exposed to the harsh microenvironment in the spinal cord of ALS. In particular, dysfunctional astrocytes and overactivated microglia in ALS may limit the survival of motor neurons generated from cell replacement therapy. On the other hand, stem cells may provide large quantities of motor neurons that can be used for studying glia-mediated toxic mechanisms and potential therapies in ALS. Here we will review methods and molecular factors for directed differentiation of stem cells into spinal motor neurons, the potential uses of these models for dissecting the mechanisms underlying glia-induced motor neuron degeneration and screening for new therapeutics aimed at protecting motor neurons in ALS, as well as discuss challenges facing the development of motor neuron replacement-based cell therapies for recovery in ALS.
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Cite this article as:
Thonhoff R. Jason, Ojeda Luis and Wu Ping, Stem Cell-Derived Motor Neurons: Applications and Challenges in Amyotrophic Lateral Sclerosis, Current Stem Cell Research & Therapy 2009; 4 (3) . https://dx.doi.org/10.2174/157488809789057392
DOI https://dx.doi.org/10.2174/157488809789057392 |
Print ISSN 1574-888X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3946 |
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