*5.1.4 Schwann cells*

*Neuroprotection - New Approaches and Prospects*

*4.2.3 Insulin-like growth factor-1*

**4.3 Stem cells**

phases of the injury.

*5.1.1 Neural stem cells*

*5.1.2 Bone marrow stem cells*

**5.1 Stem cells neural stem cells**

and SCs.

after SCI since it participates in the regulation of neuronal survival and orchestrates repairing processes in the CNS [132]. It has been previously observed that TGF-β administration reduces microglial activation and increases neuronal survival [133]. The early induction of TGF-β after SCI modulates the acute immune response, the

IGF-1 belongs to the family of insulin-related peptides, and it is the mediator of the anabolic and mitogenic activity of the growth hormone [135]. Aside from this, IGF-1 acts as a strong antioxidant [136] and pro-survival [137] factor in the CNS since it diminishes caspase-9 and elevates Bcl2 [138]. Experimental studies have shown that IGF-1 reduces edema and the upregulation of iNOS after SCI [139]. In the same way, it has been suggested that IGF-1 and erythropoietin protect against ischemic SCI in rabbits [140]. Therefore, the beneficial properties of IGF-1 make this molecule an interesting neuroprotective strategy in the acute phase of SCI.

Stem cells have also been the focus of several investigations. **Table 4** summarizes some of the neuroprotective effects exerted by stem cells like NSCs, BMSCs, OECs,

Nonpharmacological therapies with clinical studies are hence limited in acute

Transplants with human NSCs in phase I/IIa assessed the safety and neurological effects after SCI. Of 19 treated subjects, 17 were sensorimotor complete and two were motor complete and sensory incomplete. They demonstrated that 1 year after cell transplantation, there was no evidence of SC damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity [157]. Additional studies should be designed in order to afford more evidence about the efficacy of NSCs.

Regarding bone marrow stem cells (BMSC), an interesting study reported data from 20 patients with complete SCI who received transplants of BMSC. They showed improvement in motor and sensory functions [158]. In addition, a study with autologous BMSCs in three patients in the sub-acute phase of injury (<6 months of disease) demonstrated that, these cells could be safely administered through intrathecal injection in SCI patients [159]. Other study showed that 45.5% of transplanted patients presented improved neurological function. They showed some degree of improvement in sensitivity and motor function as well as in sexual function. In two patients, neuropathic pain disappeared and bladder and bowel control increased [160]. Nevertheless,

formation of glial scar and improves functional recovery [134].

**5. Nonpharmacological therapies (clinical trials)**

Pilot studies cover the acute phase of SCI.

**170**

A Phase I clinical trial with autologous human SCs was conducted to evaluate the safety of transplantation into the injury of six subjects with subacute SCI. There was no evidence of additional SC damage, mass lesion or syrinx formation. They conclude that it is feasible to identify eligible candidates, appropriately obtain informed consent, perform a peripheral nerve harvest to obtain SCs within 5–30 days of injury, and perform intra-spinal transplantation of highly purified autologous SCs within 4–7 weeks of injury [162]. Studies in acute phases using SCs are very few: therefore, more studies are needed in this area.
