Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study

Abstract Background aims. Mesenchymal stem cells/marrow stromal cells (MSC) represent a promising tool for stem cell-based clinical trials in amyotrophic lateral sclerosis (ALS). We present the results of long-term monitoring of 19 ALS patients enrolled in two phase I clinical trials of autologous MSC transplantation. Methods. Nineteen patients (11 male and eightfemale) with ALS were enrolled in two consecutive phase I clinical trials. The patients were followed-up for 6-9 months and then treated with autologous MSC isolated from bone marrow and implanted into the dorsal spinal cord with a surgical procedure. The patients were monitored regularly before and after transplantation with clinical, psychological and neuroradiologic assessments every 3 months, at the tertiary referral ALS center in Novara (Italy), until death. Results. Follow-up brain magnetic resonance imaging (MRI) revealed no structural changes (including tumor formation) relative to the baseline throughout the follow-up. There was no deterioration in the psychosocial status and all patients coped well. No clear clinical benefits were detected in these patients but the recruitment and selection of appropriate patients into larger trials will be needed to test the efficacy of the treatment. Conclusions. This study is the first to show the safety of MSC transplantation in the central nervous system during a follow-up of nearly 9 years, and is in support of applying MSC-based cellular clinical trials to neurodegenerative disorders.