Updates on Therapeutics in Clinical Trials for Spinal Cord Injuries: Key Translational Applications of Human Embryonic Stem Cells-Derived Neural Progenitors

Abstract

Injuries to the spinal cord often have devastating physiological impacts due to the organ's vital role in neuro-impulse communications between muscles and the brain. Spinal Cord Injuries (SCIs) have recently been estimated to affect up to 80,000 individuals per year worldwide, with most occurring following a traumatic event. Unfortunately, effective treatments standardised globally for patients with SCIs have not yet been established. For many years, inadequate understanding of the complexities of the Central and Peripheral Nervous Systems and Neurogenesis has limited progression towards effective cures. However, in the last century, scientific advancements have generated new paradigms for medical treatments of SCIs. Basic as well as translational studies have progressed to such an extent that many kinds of protective and regenerative therapeutics are available in clinical trials. In particular, uncovering the mechanisms responsible for controlling the pluripotent state of Human Embryonic Stem Cells (hESCs) was proved vital for recognizing the prospective role in regenerative medicine for SCIs. Elucidating knowledge of neurogenesis alongside hESCs in relation to SCIs has been crucial for critical assessments of the existing translational therapeutic strategies for SCIs.

Regenerative Therapies for Spinal Cord Injury

“…Despite active research and clinical studies, there is no effective and globally accepted standard treatment for SCI. 8 Various minimally invasive, neuroprotective, and neuroregenerative strategies using cells, biomaterials, or pharmacological agents are in various stages of preclinical research and clinical trials around the world (Table 1 and Fig. 3).…”

“…These complex events are poorly understood, hindering the development of treatments that can lead to complete recovery. 8 Present SCI treatment is mostly conservative relying on stabilization of the patient, prevention of complications, and physical rehabilitation.…”

Cellular Transplantation-Based Therapeutic Strategies for Spinal Cord Injuries: Preclinical and Clinical Updates

“…Apart from including sudden deaths from SCIs, the annual incidence rate of traumatic SCIs across the globe is 2.5-83 cases/per million population, whereas the highest ratio has been recorded in the USA [6]. Although the incidence rate of traumatic SCI is high, recently it has been reported that the incidence rate of nontraumatic SCIs is also increasing [5]. According to WHO report, there are around 250,000-500,000 people suffering annually from SCIs across the globe, where majority of the cases are due to road vehicle accidents, tumbles and other physical aggressiveness.…”

“…Till date, success has been made in cellular transplantation therapies for SCIs as their usages and procedures have now reached to clinical trials; however, these procedures are still at their early stages with no further than phase I or phase I/II clinical trials [5]. Nevertheless, all the preclinical and clinical studies have improved our understanding of repair mechanism following cellular transplantations.…”

“…In addition to neurorehabilitation, the highly established therapeutic strategies for SCIs focus on protocols that can induce early neurological protection and prevent secondary SCIs. While these procedures have revealed to encourage locomotional recovery in affected individuals with incomplete SCIs, the therapeutic outcome in patients with life-threatening incomplete and complete SCIs continues to be disappointing [5]. These kind of therapeutic failures are due to the deficiency of natural regeneration of injured axons where demyelination has occurred.…”