BackgroundImmunization with neural derived peptides (INDP) as well as scar removal—separately—have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α′-dipyridyl.ResultsDuring the chronic injury stage, two experiments were undertaken. The first experiment was aimed at testing the therapeutic effect of INDP combined with scar removal. Sixty days after therapeutic intervention, the expression of genes encoding for TNFα, IFNγ, IL4, TGFβ, BDNF, IGF1, and GAP43 was evaluated at the site of injury. Tyrosine hydroxylase and 5-hydroxytryptamine positive fibers were also studied. Locomotor evaluations showed a significant recovery in the group treated with scar removal + INDP. Moreover; this group presented a significant increase in IL4, TGFβ, BDNF, IGF1, and GAP43 expression, but a decrease of TNFα and IFNγ. Also, the spinal cord of animals receiving both treatments presented a significant increase of serotonergic and catecholaminergic fibers as compared to other the groups. The second experiment compared the results of the combined approach versus INDP alone. Rats receiving INDP likewise showed improved motor recovery, although on a lesser scale than those who received the combined treatment. An increase in inflammation and regeneration-associated gene expression, as well as in the percentage of serotonergic and catecholaminergic fibers was observed in INDP-treated rats to a lesser degree than those in the combined therapy group.ConclusionsThese findings suggest that INDP, both alone and in combination with scar removal, could modify the non-permissive microenvironment prevailing at the chronic phase of SCI, providing the opportunity of improving motor recovery.

Immunization with neural derived peptides (INDP), as well as scar removal (SR) and the use of matrices with bone marrow-mesenchymal stem cells (MSCs), have been studied separately and proven to induce a functional and morphological improvement after spinal cord injury (SCI). Herein, we evaluated the therapeutic effects of INDP combined with SR and a fibrin glue matrix (FGM) with MSCs (FGM-MSCs), on motor recovery, axonal regeneration-associated molecules and cytokine expression, axonal regeneration (catecholaminergic and serotonergic fibers), and the induction of neurogenesis after a chronic SCI. For this purpose, female adult Sprague-Dawley rats were subjected to SCI, 60 days after lesion, rats were randomly distributed in four groups: (1) Rats immunized with complete Freund's adjuvant + PBS (vehicle; PBS-I); (2) Rats with SR+ FGM-MSCs; (3) Rats with SR+ INDP + FGM-MSCs; (4) Rats only with INDP. Afterwards, we evaluated motor recovery using the BBB locomotor test. Sixty days after the therapy, protein expression of TNFα, IL-4, IL-10, BDNF, and GAP-43 were evaluated using ELISA assay. The number of catecholaminergic and serotonergic fibers were also determined. Neurogenesis was evaluated through immunofluorescence. The results show that treatment with INDP alone significantly increased motor recovery, anti-inflammatory cytokines, regeneration-associated molecules, axonal regeneration, and neurogenesis when compared to the rest of the groups. Our findings suggest that the combination therapy (SR + INDP + FGM-MSCs) modifies the non-permissive microenvironment post SCI, but it is not capable of inducing an appropriate axonal regeneration or neurogenesis when compared to the treatment with INDP alone.

Since multipotential and immunoregulatory properties were identified in mesenchymal stem cells (MSCs) in the twentieth century, they have been proposed as an effective therapy for many degenerative and traumatic diseases such as spinal cord injury (SCI). SCI is a devastating event with a high mortality rate that evokes the loss of motor and sensory functions due to neurochemical imbalance and an exacerbated immune response as a consequence of the initial mechanical damage, which in conjunction creates a hostile microenvironment that inhibits neuronal circuitry restoration. This chapter pretends to lead the reader towards the immunomodulatory, differentiation, and tissue repairing capacities of MSCs that allow them to be a valuable candidate for clinical trials. In the first section, the physiopathology of SCI will be addressed; after that, the chapter will review the general aspects of MSCs such as origin, molecular markers, and the different mechanisms by which MSCs can heal the target tissues. Finally, we will discuss clinical trials involving autologous MSC transplantation and their limitations.

Spinal cord injury (SCI) involves damage to the spinal cord causing both structural and functional changes, which can lead to temporary or permanent alterations. Even though there have been many advances in its treatment, the results of clinical trials suggest that the current therapies are not sufficiently effective.Recently, there has been a lot of interest in regulating this harmful environment by transplanting cultured cells and boosting their antiinflammatory cytokines and growth factors production. Several types of cells have been studied for SCI therapy including, Schwann cells (SC's), olfactory ensheathing cells (OECs), choroid plexus epithelial cells (CPECs), and immune cells (ICs) (lymphocytes, dendritic cells and alternative macrophage and microglia phenotypes). These treatments have shown to be promising and in this chapter, we will review the general aspects of transplanting these cells for SCI therapy as well as the neuroprotective and regenerative responses that different types of cells have reached in different SCI models. The mesenchymal stem cells (MSC) are one of the most well studied cell types; however, they were not included in this section because they will be reviewed in another chapter of this book.