Cell therapies for spinal cord injury: a review of the clinical trials and cell-type therapeutic potential

Abstract Spinal cord injury (SCI) is an as yet untreatable neuropathology that causes severe dysfunction and disability. Cell-based therapies hold neuroregenerative and neuroprotective potential, but, although being studied in SCI patients for more than two decades, long-term efficacy and safety remain unproven, and which cell types result in higher neurological and functional recovery remains under debate. In a comprehensive scoping review of 142 reports and registries of SCI cell-based clinical trials, we addressed the current therapeutical trends and critically analysed the strengths and limitations of the studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages and various types of stem cells have been tested, as well as combinations of these and other cells. A comparative analysis between the reported outcomes of each cell type was performed, according to gold-standard efficacy outcome measures like the ASIA impairment scale, motor and sensory scores. Most of the trials were in the early phases of clinical development (phase I/II), involved patients with complete chronic injuries of traumatic aetiology and did not display a randomized comparative control arm. Bone marrow stem cells and OECs were the most commonly tested cells, while open surgery and injection were the main methods of delivering cells into the spinal cord or submeningeal spaces. Transplantation of support cells, such as OECs and Schwann cells, resulted in the highest ASIA Impairment Scale (AIS) grade conversion rates (improvements in ∼40% of transplanted patients), which surpassed the spontaneous improvement rate expected for complete chronic SCI patients within 1 year post-injury (5–20%). Some stem cells, such as peripheral blood-isolated and neural stem cells, offer potential for improving patient recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may contribute highly to neurological and functional recovery. However, unbiased comparisons between the tested therapies are difficult to draw, given the great heterogeneity of the design and outcome measures used in the SCI cell-based clinical trials and how these are reported. It is therefore crucial to standardize these trials when aiming for higher value clinical evidence-based conclusions. Cell-based therapies have been studied in spinal cord injury for more than 20 years, but it remains unclear which cell types induce the greatest degree of clinical recovery. Ribeiro and Cruz