The Effect of Wharton Jelly-Derived Mesenchymal Stromal Cells and Their Conditioned Media in the Treatment of a Rat Spinal Cord Injury

Abstract

The transplantation of Wharton’s jelly derived mesenchymal stromal cells (WJ-MSCs) possesses therapeutic potential for the treatment of a spinal cord injury (SCI). Generally, the main effect of MSCs is mediated by their paracrine potential. Therefore, application of WJ-MSC derived conditioned media (CM) is an acknowledged approach for how to bypass the limited survival of transplanted cells. In this study, we compared the effect of human WJ-MSCs and their CM in the treatment of SCI in rats. WJ-MSCs and their CM were intrathecally transplanted in the three consecutive weeks following the induction of a balloon compression lesion. Behavioral analyses were carried out up to 9 weeks after the SCI and revealed significant improvement after the treatment with WJ-MSCs and CM, compared to the saline control. Both WJ-MSCs and CM treatment resulted in a higher amount of spared gray and white matter and enhanced expression of genes related to axonal growth. However, only the CM treatment further improved axonal sprouting and reduced the number of reactive astrocytes in the lesion area. On the other hand, WJ-MSCs enhanced the expression of inflammatory and chemotactic markers in plasma, which indicates a systemic immunological response to xenogeneic cell transplantation. Our results confirmed that WJ-MSC derived CM offer an alternative to direct stem cell transplantation for the treatment of SCI.

SDF-1/CXCR4 Axis-mediated Migration of Systematically Transplanted Bone Marrow Mesenchymal Stem Cells Towards the Injured Spinal Cord in a Rat Model

“…Given the fact that similar neurological injuries may occur in most cases of SCI, we have developed a standard contusion injury model of rat, in which the spinal cord is vertically contused from a de ned height and with a xed force correlating with severe neurological injury and weak functional recovery. In previous studies, cell transplantation for SCI was performed by direct injection into the injured spinal cord parenchyma [41][42][43]. However, direct injection into the spine lesion with a needle would be clinically unrealistic, and the procedure itself is potentially harmful to the parenchyma.…”

Human Wharton’s Jelly—Cellular Specificity, Stemness Potency, Animal Models, and Current Application in Human Clinical Trials

“…Because WJ-MSCs exert neuroprotective and neurotrophic effects, attempts have been made to also utilize them in spinal cord injury treatment. After the intrathecal transplantation of WJ-MSCs into rats with spinal cord injury, in several studies, the observed effects were similar, namely, an improved locomotor recovery and higher amount of spared gray matter compared to the controls [10,83,84]. Krupa et al [83] tested two dosages of cells (0.5 M and 1.5 M), which were administered one to three times in weekly intervals.…”

“…The results indicated that the effects of treatment are dose-dependent, as 1.5 M of cells provided a better outcome than 0.5 M, and this was enhanced by repeated application [83]. Chudickova et al [84] compared the results of therapy with WJ-MSCs or their culture media (CM), as beneficial effects of MSCs are exerted mainly in a paracrine manner. Compared to the treatment with stem cells, the use of culture medium improved axonal sprouting and reduced the number of reactive astrocytes; therefore, the use of CM instead of the cells themselves seems to be an attractive alternative for spinal injury treatment [84].…”

“…Chudickova et al [84] compared the results of therapy with WJ-MSCs or their culture media (CM), as beneficial effects of MSCs are exerted mainly in a paracrine manner. Compared to the treatment with stem cells, the use of culture medium improved axonal sprouting and reduced the number of reactive astrocytes; therefore, the use of CM instead of the cells themselves seems to be an attractive alternative for spinal injury treatment [84]. Mohamadi et al [10] focused on the molecular aspects of WJ-MSCs' anti-inflammatory potential.…”

Mesenchymal stromal cells as a choice for spinal cord injury treatment

“…Although most studies showed evidence that MSCs most likely act through their secretions (paracrine effect) [46][47][48] and not via their own integration/differentiation within the host tissue, some authors have reported the potential for MSCs transdifferentiation in cells of the nervous system and have shown that, after infusion into the spinal cord, these cells possibly promote regeneration of neurons because they have neuronal markers [49][50][51][52] . In vitro studies have shown that BM-MSC possess an intrinsic capacity to differentiate into neural-like and glial-like cells and express nestin, βIII-tubulin, neurofilaments, neuronspecific enolase, and glial fibrillary acidic protein (GFAP) [53][54][55] .…”