Looking backward to move forward: a meta-analysis of stem cell therapy in amyotrophic lateral sclerosis

• Type of Material: Article
• Authors: Cynthia Morata-Tarifa, Andalusian Health Ministry; Garikoitz Azkona, University of the Basque Country (UPV/EHU); Jonathan Glass, Emory University; Letizia Mazzini, University Hospital “Maggiore della Carità; Rosario Sanchez-Pernaute, Andalusian Health Ministry
• Language: English
• Date: 2021-04-01
• Publisher: Nature Research
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41536-021-00131-5
• Title of Journal or Parent Work: NPJ Regenerative Medicine
• Volume: 6
• Issue: 1
• Start Page: 20
• End Page: 20
• Grant/Funding Information: L.M. and R.S.P. would like to acknowledge BIONECA CA16122.We are grateful to Luis Lopez Navas for technical help with analysis of publication bias.; R.S.P. is the recipient of a Talentia Senior grant from the Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades of the Andalusian Government; L.M. is partly supported by the AGING Project for Department of Excellence at the Department of Translational Medicine (DIMET), Università del Piemonte Orientale, Novara, Italy.
• Keywords: Science & Technology; Technology; Cell & Tissue Engineering; Engineering; Cell Biology; Engineering, Biomedical; Life Sciences & Biomedicine
• Research Categories: Biology, Neuroscience; Biology, Cell; Health Sciences, Pathology

Abstract

Transplantation of several types of stem cells (SC) for the treatment of amyotrophic lateral sclerosis (ALS) has been evaluated in numerous Phase I/II clinical trials with inconclusive results. Here, we conducted a meta-analysis to systematically assess the outcome of SC therapy trials which report the evolution of each patient before and after cell administration. In this way, we aimed to determine the effect of the SC intervention despite individual heterogeneity in disease progression. We identified 670 references by electronic search and 90 full-text studies were evaluated according to the eligibility criteria. Eleven studies were included comprising 220 cell-treated patients who received mesenchymal (M) SC (n = 152), neural (N) SC (n = 57), or mononuclear cells (MNC: CD34, CD117, and CD133 positive cells) (n = 11). Our analyses indicate that whereas intrathecal injection of mesenchymal stromal cells appears to have a transient positive effect on clinical progression, as measured by the ALS functional rating score, there was a worsening of respiratory function measured by forced vital capacity after all interventions. Based on current evidence, we conclude that optimal cell product and route of administration need to be determined in properly controlled preclinical models before further advancing into ALS patients. In addition, in-depth understanding of disease mechanisms in subsets of patients will help tailoring SC therapy to specific targets and increase the likelihood of improving outcomes.