Human Mesenchymal Stem Cells Modulate Inflammatory Cytokines after Spinal Cord Injury in Rat

Abstract

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1β, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application.

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

“…The beneficial effects of MSCs on long-term functional recovery from spinal cord injury can be seen up to 6 months 57 or 1 year after administration. 58 However, there is evidence that MSCs survival is low at 2 weeks after injection, 36,59,60 in agreement with the present study showing evidence of transplanted MSCs survival in two out of six animals at 2 weeks. Immunosuppression may enhance MSCs survival, 61 and could be used in future experiments examining longer-term effects of BDNFMSCs transplantation.…”

Mesenchymal Stem Cell-Derived Exosomes Reduce A1 Astrocytes via Downregulation of Phosphorylated NFκB P65 Subunit in Spinal Cord Injury

“…Early intravenous delivery of MSC attenuates injury by regulating inflammation in SCI [43] and traumatic brain injury (TBI) [44][45][46]. Additionally, MSC transplantation can reduce the levels of proinflammatory cytokines, such as TNF-α and IL-1 [11,47], and inhibit NFκB signaling [12,48,49]. Moreover, MSCs are capable of switching microglia from a proinflammatory M1 phenotype towards an anti-inflammatory M2 phenotype in vitro [13] and in SCI models [50].…”

“…MSCs promote tissue repair mainly by inhibiting inflammation and activating endogenous repair mechanisms [9,10]. Previous studies demonstrated that MSCs reduce inflammatory cytokine (TNFα, IL-1, IL-6) levels [11] and inhibit NFκB activation under inflammatory conditions [12]. Additionally, MSCs are capable of directing stimulated macrophages from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype [13,14].…”

Stem cells for spine surgery

“…MSCs have been demonstrated to promote axonal regeneration and suppress demyelination [100] . Several different studies in rat models found that MSCs induce nerve regeneration, modulate the production of inflammatory cytokines such as TNF-α and IL-6 and reduce myeloperoxidase activity [101][102][103][104][105] . Menezes et al [106] hypothesized that laminin may play a pivotal role in neuron and axon preservation and regeneration after finding deposits of the glycoprotein on the lesion site …”