10. Conclusion

preclinical and clinical studies have improved our understanding of repair mechanism following cellular transplantations. As mentioned earlier, novel methods are emerging to tackle all the associated risks with cellular transplantation, where tumorigenesis can be prevented by using specialized protocols [126]. Up till now, even after reaching into clinical trials, fundamental associations between locomotory functional development and specific mechanisms in SCIs have rarely been achieved [145]. Yet, some studies have reported clinical success by using cellular transplantation therapies for SCIs. One of such study has been conducted in 2003, where a clinician directly transplanted OECs derived from aborted fetuses in Chinese hospital. In this contentious experiment, 171 spinal cord-injured patients were reported to have recovered from SCIs without any associated risk [146, 147]. Two years later, a Korean research division claimed that umbilical cord blood-derived MSCs have the ability to recover locomotory function in a patient who was suffering from a complete disability for several years [55]. The claims made in these studies received controversial responses because they were associated with ethical challenges, greater risk association and still require appropriate and accurate clinical confirmations [147]. Nonetheless, cellular transplantation therapies for SCIs are becoming more exciting and interesting, especially when research studies of lower immune rejections and preventing teratoma formation are

In the current era of regenerative medicine, cell-based transplantation therapies have advanced our approaches to an extent that these therapies soon will be capable of treating subacute and chronic SCIs in the very near future. The ongoing improvements and assessments of associated risks with cellular transplantation, improved relevance of preclinical models, long-term enhanced recovery, in vivo tracking of transplanted cells and preventing teratoma formations are advancing the future aspects of these therapies for SCIs [5, 126, 145]. Cells that are derived from hESCs and iPSCs are showing promising results in preclinical and clinical trials, indicating their dominance in the prospective field of personalized and regenerative medicines. In particular, the iPSC-derived cell progeny that is disease and patient-specific, is evidently the best option as it carries lower immune rejection and is limited to particular cell types [149]. In addition to the ongoing comprehensive neuroregenerative and neuroprotective therapeutic strategies for SCIs [5], newer technologies are evolving including neuroscience-based computational and robotic rehabilitational therapies. In 2014, a group of Swiss scientists reported an innovative discovery for treatment of complete SCI using neuroscience modulation-based therapeutic approach to control spinal sensorimotor network, without involving cellular transplantation techniques. In this study, an electric stimulus-based procedure was used to assist a non-standing paralytic rat model with complete injured spinal cord to move the paralyzed feet again and even climbed staircases [150]. The neurorobotic techniques-based therapies for SCIs are also emerging, as recently being reported where a volunteer-driven exoskeleton was used as an innovative robotic device for rehabilitation in chronic SCIs [151]. These exoskeleton

paving the ways for future regenerative research [126, 148].

9. Future prospects

142 Essentials of Spinal Cord Injury Medicine

Spinal cord injury, a devastating condition where patient feels sharpest pain shooting from vertebrae through the neck up head and subsequent paralysis has unfortunately no proper treatment. In recent times across the globe, a renewed attention has been diverted to find and develop a complete treatment for SCIs. In addition to neuroregenerative, neuroprotective and neuro-computational strategies, cellular transplantations are considered the most relevant, inspiring and encouraging therapies for treatment of SCIs. To date, numerous preclinical and clinical studies have confirmed cellular regeneration and locomotory functional recovery from SCIs following cellular transplantation. Instead of direct transplantation of hESCs and iPSCs, their derived cell population is the most preferred type of cells for successful transplantational recovery, as evident from their extents into the clinical trials. Novel approaches have revealed to specifically generate desired cell type, track the transplanted cells in vivo and prevent associated risks of tumorigenesis and loss of locomotional functions. Accomplishments from these newer improved strategies are opening new avenues for future research to completely cure SCIs.
