Advances, Challenges, and Perspectives in Translational Stem Cell Therapy for Amyotrophic Lateral Sclerosis

Research output: Contribution to journalReview article

Abstract

Finding an effective therapeutic approach is a primary goal for current and future research for amyotrophic lateral sclerosis (ALS), a fatal neurological disease characterized by degeneration and loss of upper and lower motor neurons. Transplantation approaches based on stem cells have been attempted in virtue of their potential to contrast simultaneously different ALS pathogenic aspects including either the replacement of lost cells or the protection of motor neurons from degeneration and toxic microenvironment. Here, we critically review the recent translational research aimed at the assessment of stem cell transplantation safety and feasibility in the treatment of ALS. Most of these efforts aim to exert a neuroprotective action rather than cell replacement. Critical aspects that emerge in these studies are the need for the identification of the most effective therapeutic cell source (mesenchymal stem cells, immune, or neural stem cells), the definition of the optimal injection site (cortical area, spinal cord, or muscles) with a suitable administration protocol (local or systemic injection), and the analysis of therapeutic mechanisms, which are necessary steps in order to overcome the hurdles posed by previous in vivo human studies. New perspectives will also be offered by the increasing number of induced pluripotent stem cell-based therapies that are now being tested in clinical trials. A thorough analysis of recently completed trials is the foundation for continued progress in cellular therapy for ALS and other neurodegenerative disorders.

Original languageEnglish
Pages (from-to)6703-6715
Number of pages13
JournalMolecular Neurobiology
Volume56
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

Fingerprint

Amyotrophic Lateral Sclerosis
Cell- and Tissue-Based Therapy
Stem Cells
Motor Neurons
Therapeutics
Induced Pluripotent Stem Cells
Nerve Degeneration
Injections
Translational Medical Research
Cytoprotection
Neural Stem Cells
Poisons
Stem Cell Transplantation
Mesenchymal Stromal Cells
Neurodegenerative Diseases
Spinal Cord
Transplantation
Clinical Trials
Safety
Muscles

Keywords

  • Amyotrophic lateral sclerosis
  • Induced pluripotent stem cells
  • Mesenchymal stem cells
  • Motor neuron
  • Neural stem cells
  • Regulatory T cells
  • Stem cell transplantation

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Advances, Challenges, and Perspectives in Translational Stem Cell Therapy for Amyotrophic Lateral Sclerosis. / Abati, Elena; Bresolin, Nereo; Comi, Giacomo; Corti, Stefania.

In: Molecular Neurobiology, Vol. 56, No. 10, 01.10.2019, p. 6703-6715.

Research output: Contribution to journalReview article

@article{0c288ab2eafc4c13a6012ca8c85a93dc,
title = "Advances, Challenges, and Perspectives in Translational Stem Cell Therapy for Amyotrophic Lateral Sclerosis",
abstract = "Finding an effective therapeutic approach is a primary goal for current and future research for amyotrophic lateral sclerosis (ALS), a fatal neurological disease characterized by degeneration and loss of upper and lower motor neurons. Transplantation approaches based on stem cells have been attempted in virtue of their potential to contrast simultaneously different ALS pathogenic aspects including either the replacement of lost cells or the protection of motor neurons from degeneration and toxic microenvironment. Here, we critically review the recent translational research aimed at the assessment of stem cell transplantation safety and feasibility in the treatment of ALS. Most of these efforts aim to exert a neuroprotective action rather than cell replacement. Critical aspects that emerge in these studies are the need for the identification of the most effective therapeutic cell source (mesenchymal stem cells, immune, or neural stem cells), the definition of the optimal injection site (cortical area, spinal cord, or muscles) with a suitable administration protocol (local or systemic injection), and the analysis of therapeutic mechanisms, which are necessary steps in order to overcome the hurdles posed by previous in vivo human studies. New perspectives will also be offered by the increasing number of induced pluripotent stem cell-based therapies that are now being tested in clinical trials. A thorough analysis of recently completed trials is the foundation for continued progress in cellular therapy for ALS and other neurodegenerative disorders.",
keywords = "Amyotrophic lateral sclerosis, Induced pluripotent stem cells, Mesenchymal stem cells, Motor neuron, Neural stem cells, Regulatory T cells, Stem cell transplantation",
author = "Elena Abati and Nereo Bresolin and Giacomo Comi and Stefania Corti",
year = "2019",
month = "10",
day = "1",
doi = "10.1007/s12035-019-1554-x",
language = "English",
volume = "56",
pages = "6703--6715",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press Inc.",
number = "10",

}

TY - JOUR

T1 - Advances, Challenges, and Perspectives in Translational Stem Cell Therapy for Amyotrophic Lateral Sclerosis

AU - Abati, Elena

AU - Bresolin, Nereo

AU - Comi, Giacomo

AU - Corti, Stefania

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Finding an effective therapeutic approach is a primary goal for current and future research for amyotrophic lateral sclerosis (ALS), a fatal neurological disease characterized by degeneration and loss of upper and lower motor neurons. Transplantation approaches based on stem cells have been attempted in virtue of their potential to contrast simultaneously different ALS pathogenic aspects including either the replacement of lost cells or the protection of motor neurons from degeneration and toxic microenvironment. Here, we critically review the recent translational research aimed at the assessment of stem cell transplantation safety and feasibility in the treatment of ALS. Most of these efforts aim to exert a neuroprotective action rather than cell replacement. Critical aspects that emerge in these studies are the need for the identification of the most effective therapeutic cell source (mesenchymal stem cells, immune, or neural stem cells), the definition of the optimal injection site (cortical area, spinal cord, or muscles) with a suitable administration protocol (local or systemic injection), and the analysis of therapeutic mechanisms, which are necessary steps in order to overcome the hurdles posed by previous in vivo human studies. New perspectives will also be offered by the increasing number of induced pluripotent stem cell-based therapies that are now being tested in clinical trials. A thorough analysis of recently completed trials is the foundation for continued progress in cellular therapy for ALS and other neurodegenerative disorders.

AB - Finding an effective therapeutic approach is a primary goal for current and future research for amyotrophic lateral sclerosis (ALS), a fatal neurological disease characterized by degeneration and loss of upper and lower motor neurons. Transplantation approaches based on stem cells have been attempted in virtue of their potential to contrast simultaneously different ALS pathogenic aspects including either the replacement of lost cells or the protection of motor neurons from degeneration and toxic microenvironment. Here, we critically review the recent translational research aimed at the assessment of stem cell transplantation safety and feasibility in the treatment of ALS. Most of these efforts aim to exert a neuroprotective action rather than cell replacement. Critical aspects that emerge in these studies are the need for the identification of the most effective therapeutic cell source (mesenchymal stem cells, immune, or neural stem cells), the definition of the optimal injection site (cortical area, spinal cord, or muscles) with a suitable administration protocol (local or systemic injection), and the analysis of therapeutic mechanisms, which are necessary steps in order to overcome the hurdles posed by previous in vivo human studies. New perspectives will also be offered by the increasing number of induced pluripotent stem cell-based therapies that are now being tested in clinical trials. A thorough analysis of recently completed trials is the foundation for continued progress in cellular therapy for ALS and other neurodegenerative disorders.

KW - Amyotrophic lateral sclerosis

KW - Induced pluripotent stem cells

KW - Mesenchymal stem cells

KW - Motor neuron

KW - Neural stem cells

KW - Regulatory T cells

KW - Stem cell transplantation

UR - http://www.scopus.com/inward/record.url?scp=85071785673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071785673&partnerID=8YFLogxK

U2 - 10.1007/s12035-019-1554-x

DO - 10.1007/s12035-019-1554-x

M3 - Review article

C2 - 30911936

AN - SCOPUS:85071785673

VL - 56

SP - 6703

EP - 6715

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 10

ER -