ABSTRACT
Introduction: Spinal cord injury (SCI) is a devastating condition, where regenerative failure and cell loss lead to paralysis. The heterogeneous and time-sensitive pathophysiology has made it difficult to target tissue repair. Despite many medical advances, there are no effective regenerative therapies. As stem cells offer multi-targeted and environmentally responsive benefits, cell therapy is a promising treatment approach.
Areas covered: This review highlights the cell therapies being investigated for SCI, including Schwann cells, olfactory ensheathing cells, mensenchymal stem/stromal cells, neural precursors, oligodendrocyte progenitors, embryonic stem cells, and induced pluripotent stem cells. Through mechanisms of cell replacement, scaffolding, trophic support and immune modulation, each approach targets unique features of SCI pathology. However, as the injury is multifaceted, it is increasingly recognized that a combinatorial approach will be necessary to treat SCI.
Expert opinion: Most preclinical studies, and an increasing number of clinical trials, are finding that single cell therapies have only modest benefits after SCI. These considerations, alongside issues of therapy cost-effectiveness, need to be addressed at the bench. In addition to exploring combinatorial strategies, researchers should consider cell reproducibility and storage parameters when designing animal experiments. Equally important, clinical trials must follow strict regulatory guidelines that will enable transparency of results.
Article highlights
Cell therapy is an attractive therapeutic approach for SCI with the potential to mediate recovery through cell replacement, scaffolding, trophic support, and immune modulation.
There are several diverse cell transplantation strategies actively investigated, including SCs, OEGs/OECs, MSCs, NSCs/NPCs, OPCs, ESCs, and iPSCs.
Various challenges, ranging from cell safety and efficacy to cost-effectiveness and regulation, need to be addressed for successful clinical and/or commercial deployment.
A combinatorial regimen is most likely to target the multi-factorial nature of SCI.
Increased research transparency, at the basic science and clinical levels, will help drive progress in the field.
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Declaration of interest
A Badner is supported by funds from the Canadian Institutes of Health Research (CIHR) Training Program in Regenerative Medicine (TPRM), the Ontario Graduate Scholarship (OGS) and the James F. Crothers Family Fellowship in Peripheral Nerve Damage. MG Fehlings receives support from the Halbert Chair in Neural Repair and Regeneration and Dezwirek 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.