5.1.2. Fetal brain-derived human central nervous system stem cell/neural precursors

The skill of isolation, proliferation and genetic manipulation of ESCs is one of the most important accomplishments in experimental stem cells biology [46]. An isolation of ESCs and their controlled proliferation into neural precursors population has been achieved in variety of preclinical models. After transplantation of ESC-derived neural precursors into the CNS of animal models, the cells have been observed to assimilate well into the recipient tissue and have also shown to improve locomotional recovery in injured rat spinal cord [46, 47]. To evaluate in vivo differentiation of hESC-derived neural precursors, a study has shown that these cells were able to integrate, migrate and differentiate into a host tissue [40]. After the preclinical validations and successful outcomes from ESC-derived neural precursors, they are being evaluated in clinical trials with a name HuCNS-SC. The HuCNS-SCs are highly purified fetal brain-derived human CNS stem cells, which have been shown to promote neuroprotection after SCIs [48]. In addition to its use for SCIs, HuCNS-SCs have been used in clinical trials for other disorders including neuronal ceroid lipofuscinosis, age-related macular degeneration and Pelizaeus-Merzbacher disease [48–51]. Following transplantation, HuCNS-SCs are shown to differentiate into neurons and glia and also retained semipermanent survival ability in host tissues. They have been recently evaluated in phase I/II clinical trials (NCT01321333) for safety and preliminary efficacy in patients with subacute SCI via intramedullary transplantation into thoracic spinal cord region [44]. In the clinical outcome from this trial (NCT01321333) that involved 5-year follow-up period, absolutely no safety issues have been documented [52].

### 5.1.3. Umbilical cord blood-derived mononuclear cells

Transplantation of human umbilical cord blood-derived stem cells has been reported to migrate well and promote therapeutic recovery from neurological injuries such as stroke and SCIs [53]. Following intravenous administration of human umbilical cord blood-derived stem cells, a study has demonstrated that the transplanted cells were able to improve behavioral properties of induced SCI [53]. Another preclinical study has reported functional locomotory effect following the administration of human umbilical cord blood cells in combination with brain-derived neutrophic factor into the SCI rat model [54]. In addition to preclinical studies on animal models, a case study on human (37-year-old female) patient with SCI has reported an injection of human umbilical cord blood-derived stem cells. In this study, it was shown that cell transplantation ameliorates sensory perception and movement of body parts, based on functional and morphological analysis [55]. Recently, the transplantation of umbilical cord bloodderived mononuclear cells (UCBMC) has been tested in phase I/II clinical trials (NCT01354483; NCT01471613) for treatment of acute, subacute and chronic SCIs in combination with neuroprotective agents such as lithium carbonate and methylprednisolone [44]. Following transplantation, these cells have been observed to decrease sensimotor injury and other associated cerebral deficiency [56]. In one of the clinical trial outcomes involving UCBMC (NCT01354483), the cellular transplantation was observed to be safe while some recipients were appeared to regain sensorimotor function [57].
