Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes

Abstract

In this study, we examined the efficacy of human umbilical cord blood mononuclear cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using adenoviral vectors, on posttraumatic regeneration after transplantation into the site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by transplantation of nontransduced hUCB-MCs, we observed an improvement in H (latency period, LP) and M(Amax) waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M wave and LP of both the M and H waves. The ratio between Amax of the H and M waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs. Spared tissue and myelinated fibers were increased at day 30 after SCI and transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF and GNDF genes significantly increased the number of spared myelinated fibers (22-fold, P > 0.01) in the main corticospinal tract compared to the nontransduced ones. HNA+ cells with the morphology of phagocytes and microglia-like cells were found as compact clusters or cell bridges within the traumatic cavities that were lined by GFAP+ host astrocytes. Our results show that hUCB-MCs transplanted into the site of SCI improved regeneration and that hUCB-MCs genetically modified with the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.

Co-administration of human adipose-derived stem cells and low-level laser to alleviate neuropathic pain after experimental spinal cord injury

“…Transplantation of various cells after SCI has led to increase in GDNF mRNA expression [58][59][60]. GDNF increases survival of motor and sensory neurons, improves motor function, induces neurogenesis and axonal growth, enhances myelination, and alleviates pain (analgesia effect) [35,[58][59][60][61][62].…”

Glial-derived neurotrophic factor is essential for blood-nerve barrier functional recovery in an experimental murine model of traumatic peripheral neuropathy

“…There is some evidence that strategies involving increased local expression of VEGF and GDNF resulted in more rapid and effective repair in a spinal cord tissue injury model. 66 Human endoneurial endothelial cells are also known to express connective tissue growth factor in vitro and in situ, 48 implying that a healthy functional BNB may contribute to local wound healing and restoration of endoneurial homeostasis and its fibrous architecture following injury. Restoring BNB function may be a necessary requisite to re-establish the tightly regulated Figure 9.…”

Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix Promotes Structural and Functional Recovery Following Spinal Cord Injury in Rats

“…Electrophysiological tests were performed on intact rats and control/experimental rats 2 and 11 weeks after SCI as previously described ( Mukhamedshina et al, 2017a ). The animal’s neuromotor function was assessed by stimulating electromyography.…”