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.