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Molecular Neurobiology

, Volume 56, Issue 10, pp 6703–6715 | Cite as

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

  • Elena Abati
  • Nereo Bresolin
  • Giacomo Comi
  • Stefania CortiEmail author
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.

Keywords

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

Notes

Acknowledgments

We thank the Associazione Amici del Centro Dino Ferrari for its support. The figure was modified from images from Servier Medical Art, licensed under a Creative Common Attribution 3.0 Generic License. http://smart.servier.com/

Funding information

The following grant supports are gratefully acknowledged: Italian Ministry of Health-RF-2016-02362317 and AFM-Telethon-2015, “Optimized Transplantation of hiPSC-derived LeX+CXCR4+VLA4 neural stem cells as a therapy for SMARD1” to GPC, and CROSS-NEUROD Grant ID: 778003 to SC.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience SectionUniversity of MilanMilanItaly
  2. 2.Neurology UnitFoundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, Neurology UnitFoundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of MilanMilanItaly

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