How can clinical safety and efficacy concerns in stem cell therapy for spinal cord injury be overcome?

ABSTRACTIntroduction Spinal cord injury (SCI) can lead to severe neurological dysfunction. Despite scientific and medical advances, clinically effective regenerative therapies including stem cells are lacking for SCI.Areas covered This paper discusses translational challenges related to the safe, effective use of stem cells for SCI, with a focus on mesenchymal stem cells (MSCs), neural stem cells (NSCs), Schwann cells (SCs), olfactory ensheathing cells (OECs), oligodendrocyte precursor cells (OPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). We discuss approaches to enhance the efficacy of cell-based strategies by i) addressing patient heterogeneity and enhancing patient selection; ii) selecting cell type, cell source, cell developmental stage, and delivery technique; iii) enhancing graft integration and mitigating immune-mediated graft rejection; and iv) ensuring availability of cells. Additionally, we review strategies to optimize outcomes including combinatorial use of rehabilitation and discuss ways to mitigate potential risks of tumor formation associated with stem cell-based strategies.Expert opinion Basic science research will drive translational advances to develop stem cell-based therapies for SCI. Genetic, serological, and imaging biomarkers may enable individualization of cell-based treatments. Moreover, combinatorial strategies will be required to enhance graft survival, migration and functional integration, to enable precision-based intervention.KEYWORDS: Clinical trialssafety and efficacystem cellsspinal cord injuryregenerative therapies Article highlights There are various translational challenges in developing safe and effective stem cell-based strategies for traumatic spinal cord injury (SCI).The types of stem cells currently being investigated for their potential to treat SCI include mesenchymal stem cells, neural stem cells, Schwann cells, olfactory ensheathing cells, oligodendrocyte precursor cells, embryonic stem cells, and induced pluripotent stem cells.To enhance the efficacy of cell-based strategies, we need to address patient heterogeneity, optimize cell type and source, mitigate immune-mediated rejection, improve graft integration, and ensure the availability of cells.Additionally, successful cell-based therapies should also strive to improve the viability of stem cells while ensuring genetic safety to mitigate risks of tumor formation.To evaluate treatment effects and promote positive patient outcomes, we need to capture the beneficial effects of interventions and implement measures to support individual patients, such as rehabilitation.Declaration of interestN Hejrati is supported by the Research Fund of the University of Basel for Excellent Junior Researchers. MG Fehlings is supported by the Robert Campeau Family Foundation/Dr. C.H. Tator Chair in Brain and Spinal Cord Research at UHN and The Krembil Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.