The Effect of Human Mesenchymal Stem Cells Derived from Wharton’s Jelly in Spinal Cord Injury Treatment Is Dose-Dependent and Can Be Facilitated by Repeated Application

Abstract

Human mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis. Endogenous gene expression (Gfap, Casp3, Irf5, Cd86, Mrc1, Cd163) was studied with quantitative Real-time polymerase chain reaction (qRT PCR). Significant recovery of functional outcome was observed in all of the treated groups except for the single application of the lowest number of cells. Histochemical analyses revealed a gradually increasing effect of grafted cells, resulting in a significant increase in the number of GAP43+ fibers, a higher amount of spared gray matter and reduced astrogliosis. mRNA expression of macrophage markers and apoptosis was downregulated after the repeated application of 1.5 million cells. We conclude that the effect of hWJ-MSCs on spinal cord regeneration is dose-dependent and potentiated by repeated application.

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

“…MSCs can mediate anatomical improvement in the subacute phase after SCI through anti-inflammatory activity, glial scar reduction, and cell bridging effects [50,60]. Our results suggest that MSCs are able to prevent secondary injury by contributing to astroglia suppression, consistent with the results of other studies of MSC transplantation in SCI [61][62][63]. We observed greater reduction of astroglial activation caudally from the injury epicenter after AD-MSCs application compared to other sources of MSCs and the control groups.…”

A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential

“…The broad spectrum of pathologies where MSCs can be applied, either as an injectable suspension or within a scaffold or hydrogels, has been reported elsewhere and includes wounds 1,2 , bone and cartilage defects 3 , graft-versus-host disease 4 , cardiovascular 5,6 or neural disorders (multiple sclerosis, stroke, spinal cord injury etc.) [7][8][9] . Previously we have shown that MSC transplantation has a positive impact on neural tissue regeneration in spinal cord injury models 8,10,11 or a protective effect in amyotrophic lateral sclerosis (SOD1G93A) rats 7 .…”

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.…”

“…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].…”

“…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.…”