Clinical Trials Using Mesenchymal Stem Cells for Spinal Cord Injury: Challenges in Generating Evidence

Abstract

Spinal cord injury (SCI) remains an important public health problem which often causes permanent loss of muscle strength, sensation, and function below the site of the injury, generating physical, psychological, and social impacts throughout the lives of the affected individuals, since there are no effective treatments available. The use of stem cells has been investigated as a therapeutic approach for the treatment of SCI. Although a significant number of studies have been conducted in pre-clinical and clinical settings, so far there is no established cell therapy for the treatment of SCI. One aspect that makes it difficult to evaluate the efficacy is the heterogeneity of experimental designs in the clinical trials that have been published. Cell transplantation methods vary widely among the trials, and there are still no standardized protocols or recommendations for the therapeutic use of stem cells in SCI. Among the different cell types, mesenchymal stem/stromal cells (MSCs) are the most frequently tested in clinical trials for SCI treatment. This study reviews the clinical applications of MSCs for SCI, focusing on the critical analysis of 17 clinical trials published thus far, with emphasis on their design and quality. Moreover, it highlights the need for more evidence-based studies designed as randomized controlled trials and potential challenges to be addressed in context of stem cell therapies for SCI.

Adverse events of cell therapy clinical trials in human chronic spinal cord injury, a systematic review and meta-analysis

“…The CSF leak, wound infection, and constipation were the more common severe AEs in our review. The CSF leakage has been more common severe AE in other studies [ 56 , 59 , 60 ]. The wound infection with Staph.…”

“…In de Araújo, L.T. et al., study, the most common side events were moderate headache and pain at the site of the lesion [ 56 ]. In Kvistad CE.…”

Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats

“…Complementary therapeutic approaches, including cell therapy [7,8], glial scar digestion, neurotrophic factor delivery, laser therapy [9][10][11], and electrical stimulation of surrounding tissue as well as clinical rehabilitation, are being developed to achieve nerve fiber regeneration and functional restoration in SCI. But the extent of neural tissue destruction in chronic SCI in humans, with entire segments of the spinal cord replaced by fluid-filled cysts, remains a critical concern.…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…More than 500 clinical research on MSC is underway in the world for various target diseases, including rheumatoid arthritis, systemic lupus erythematosus, Crohn’s disease, myocardial infarction, Parkinson’s disease, spinal cord injury, osteoarthritis, and graft-versus-host disease (GVHD) [ 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 ]. MSCs other than those derived from bone marrow are also being clinically applied.…”