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.
Highlights
Spinal cord injury (SCI) represents a severe trauma for which an effective treatment is still not available
We have shown that mesenchymal stromal cell (MSCs) derived from bone marrow (BM), adipose tissue (AT) or Wharton’s jelly (WJ) differ in their secretion of neurotrophic, neuroprotective or antioxidative factors [31], all of these cell populations shared the capability of secreting important neuroregulatory molecules [12]
We have previously demonstrated that intrathecal transplantation of BM-MSCs and Wharton’s jelly derived mesenchymal stromal cells (WJ-MSCs) had a positive impact on neural tissue regeneration in SCI models, and that this effect increased with the dose [7,8]
Summary
Spinal cord injury (SCI) represents a severe trauma for which an effective treatment is still not available. A broad spectrum of strategies have been used in order to reduce oxidative stress, prevent apoptosis, promote the function of spared axons, induce new axon growth or replace lost cells using stem cell transplantation [1,2,3] In this regard, stem cell therapy and in particular, mesenchymal stromal cell (MSCs) transplantation, has been proposed as an effective, safe and feasible alternative method for SCI repair [4,5]. Transplantation of MSC secretomes, called conditioned medium (CM), or purified MSC-derived extracellular vesicles, have shown similar therapeutic effects and functional improvement as direct stem cell transplantation in various disease models [13]. Intravenous administration of MSC-derived exosomes or extracellular vesicles revealed pro-regenerative effects including functional recovery, enhanced axonal regeneration, pro-angiogenic properties, attenuation of neuronal cell apoptosis and lesion size and suppression of glial scar formation and inflammation [25,26,27]. O2.uRrerseuslutslts have proven that CM derived from human WJ-MSCs improved repair after SCI in rats and that this effect is comparable or even superior to direct human cell transplantation
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