5.3.1. Autologous human Schwann cells

Wharton's Jelly expanded MSCs with Placebo/XCEL-UMC-BETA intervention is being evaluated against thoracic SCIs in phase 1/2a, which is expected to be completed in April, 2020 (NCT03003364). Another phase 1/2 clinical trial that was testing the use of UC-MSCs in combination with bone marrow mononuclear cells was expected to complete in October 2019; however, it was withdrawn prior to enrolment (NCT02237547). One of the ongoing phase 1/2 clinical trial that purely involves the use of allogenic UC-MSCs is evaluating its safety and viability using intrathecal injections. This trial involves patients with complete or incomplete cervical and

In comparison to the umbilical cord blood, another source that has been reported to hold more number of MSCs is adipose tissue. It had been shown that 100% of MSCs can be isolated from adipose tissues compare to 63% of isolation from umbilical cord blood [82]. Since the adiposederived MSCs have been recognized by immunosuppressant characteristics and less immunogenic behavior, they have been considered as a potential source of treatment for SCIs [84]. A study has reported that after an intravenous administration of human adipose-derived MSCs in murine models (Balb/c-nu nude mice) and humans (n = 8) clinical trial (NCT01274975) for SCIs, no safety issues were seen and also the transplanted cells did not develop teratomas [85]. The use of adipose-derived MSCs has been evaluated in phase I and I/II clinical trials for treatment of different SCIs [1, 44]. A phase 1 clinical trial that has been completed in October 2012 reported that co-administration of autologous adipose-derived MSCs' differentiated neuronal cells (N-Ad-MSC) and hematopoietic in patients' CSF is safe and feasible treatment option for SCIs [86]. Another phase 1/2 clinical trial has evaluated adipose-derived MSCs in patients with acute SCIs, which was expected to be completed in 2015; however, the clinical

A specific cell progeny can be derived from MSCs, which has been tested in different clinical trials that mainly involve MSC-derived neural stem cell (NSC) population. In one of the most recent phase 1 clinical trials, human spinal cord-derived neural stem cells population has been used for transplantation to treat patients with chronic cervical and thoracic SCIs. The clinical outcome form this trial is still pending as the trial is expected to be completed in December 2022 (NCT01772810). A phase 1/2 clinical trial is currently evaluating MSCs-autologous NSC transplantation together with RMx Biomatrix (3D biomatrix) as scaffold for treatment of acute, sub-chronic and chronic lumbar and thoracic SCIs, which is expected to be completed in December 2018 (NCT02326662). Another phase 1/2 clinical trial that is currently ongoing for treatment of patients with cervical and throracic SCIs is utilizing the transplantation of MSCs-NSCs in combination with "NeuroRegen" scaffolds. This trial is expected to be completed in June 2018 (NCT02688049).

In addition to other type of cells, the most relevant cell types for treatment of SCIs are the peripheral myelinating cells, which are mainly damaged during primary and secondary injury

thoracic SCIs, which is expected to be completed in December 2018 (NCT02481440).

5.2.3. Autologous adipose-derived MSCs

136 Essentials of Spinal Cord Injury Medicine

outcomes are still pending (NCT02034669).

5.2.4. MSC-derived neural stem cells

5.3. Peripheral myelinating cells

Schwann cells have been reported to display significant flexibility in performing a wide range of functions in nervous system through major involvement in ensheating and myelination of axons. Schwann cells are playing crucial regenerative role in supporting regeneration of axons in the PNS, which indicates that the uses of Schwann cell transplantation and autografting will offer regenerative role in damaged CNS [87]. Different studies have reported the differentiation of adult precursor cells into Schwann cells, including a study where precursor cells isolated from skin were able to produce myelinating Schwann cells. Upon transplantation, these Schwann cells were able to improve remyelination and supported locomotional recovery from contusion SCI [88]. Following transplantation, the Schwann cells are characterized by remyelination of damaged axons and maintaining an environment favorable for axonal regrowth by secreting important growth and trophic factors [89]. One of a renowned study has shown that a combination of Schwann cell transplantation and regulation of cyclic adenosine monophosphate (cAMP) levels by using rolipram and/or a cAMP analog (db-cAMP), might improve the overall regenerative roles of Schwann cells in treatment of SCIs [90].

In clinical trials, the autologous human Schwann cells have been evaluated in phase I trials (NCT01739023; NCT02354625) for chronic and subacute SCIs [44]. In one of the most recently completed phase 1 clinical trial, transplantation of autologous human Schwann cells (ahSC) has been evaluated in patients with subacute lumbar SCIs (NCT01739023). In the clinical outcome following 1-year assessment, no signs were observed for serious side effects that could be specifically associated to the nerve harvest, cellular transplantation protocol, or to the transplanted cells in lesion site [91]. Another phase 1 clinical trial that is utilizing ahSCs in combination with rehabilitation to treat chronic lumbar and thoracic SCIs is expected to be completed in January 2018 (NCT02354625).
