8. Success story and controversies of cell transplantation in patients with SCIs

Researchers in the field of cellular therapy and regenerative medicines are restraining to directly inject hESCs or iPSCs in humans, but rather more inclined to evaluate hESCs- or human iPSC-derived cell population, i.e. ODPs, HuCNS-SC, Schwann cells, olfactory ensheathing cells, umbilical cord blood mononuclear cells, autologous BMSCs and umbilical cord blood- and adipose-derived MSCs, as evident from the recent and ongoing clinical trials —Table 1. In contrast to direct transplantation of ESCs or iPSCs, direct administration of the above-mentioned derived cells is only limited to form single-specific cell progeny and also possesses lower risk of developing teratomas in host specie [144].

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

robotic devices work as a wearable outfit that regulates the external movements by detecting internal nerve signals in patients with SCIs. However, such neuroscience-based computational and robotic rehabilitation therapies are evolving for treatment of SCIs, yet they are in the initial phases of development and do not offer a complete cure to fully repair and regenerate injured spinal cord. Nevertheless, any sort of therapeutic strategy that can rehabilitate and improve functional recovery will always be considered a therapy-of-future for SCIs, as being phrased "something is better than nothing." In a nutshell, the only therapeutic approach that could be able to completely cure SCIs in near future is the use of cell-based transplantation strategies.

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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

We are thankful to the Deanship of Scientific Research, King Abdulaziz University (DSR) and King Abdulaziz Center for Science and Technology (KACST), Saudi Arabia, for their technical and financial support in our various research projects. We would also like to acknowledge "Higher Education Commission" of Pakistan and "IBMS, Khyber Medical University" for their

10. Conclusion

cure SCIs.

Acknowledgements

financial support.

Conflict of interest

The authors declare that there are no conflicts of interest.
