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

Spinal cord injury (SCI) is a 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 it is still debated which cell types result in higher neurological and functional recovery. In a comprehensive scoping review of 142 reports and registries of SCI cell-based clinical trials, we addressed the current therapeutical trends and critically analyzed the strengths and limitations of the studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages, and various types of stem cells (SCs) 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 (AIS), 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 etiology, and did not display a randomized comparative control arm. Bone marrow SCs and OECs were the mainly used cells, while open surgery and injection were the most common methods, delivering cells into the spinal cord or submeningeal spaces. Transplantation of support cells, such as OECs and Schwann cells, resulted in the highest AIS grade conversion rates (improvements in ∼40% of transplanted patients), which surpasses the spontaneous improvement rate expected for complete chronic SCI patients within one-year post-injury (5-20%). Some stem cells, such as peripheral blood-isolated ones (PB-SCs) and Neural SCs (NSCs) and also present potential for improving patients' recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may highly contribute 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 clinical evidence-based conclusions of higher value.