Current Options for Cell Therapy in Spinal Cord Injury

Vismara, Irma; Papa, Simonetta; Rossi, Filippo; Forloni, Gianluigi; Veglianese, Pietro

doi:10.1016/j.molmed.2017.07.005

Cited by 162 publications

(144 citation statements)

References 155 publications

(159 reference statements)

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“…Several preclinical experiments report the efficacy of stem cell therapy to improve motor activity when administrated into murine SCI models obtained via compression, contusion, or transaction of the spinal cord (Dasari, Veeravalli, & Dinh, ). Moreover, MSCs can provide immunomodulation and trophic support in SCI, as they can release many potential beneficial factors at the damaged tissue site (Vismara, Papa, Rossi, Forloni, & Veglianese, ).…”

Section: Discussionmentioning

confidence: 99%

Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury

Mammana

Gugliandolo

Cavalli

et al. 2019

J Tissue Eng Regen Med

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Spinal cord injury (SCI) is a neurological disorder that arises from a primary acute mechanical lesion, followed by a pathophysiological cascade of events that leads to further spinal cord tissue damage. Several preclinical and clinical studies have highlighted the ability of stem cell therapy to improve long‐term functional recovery in SCI. Previously, we demonstrated that moringin (MOR) treatment accelerates the differentiation process in mesenchymal stem cells inducing an early up‐regulation of neural development associated genes. In the present study, we investigated the anti‐inflammatory, anti‐apoptotic, and regenerative effects of gingival mesenchymal stem cells (GMSCs) pretreated with nanostructured liposomes enriched with MOR in an animal model of SCI. SCI was produced by extradural compression of the spinal cord at levels T6–T7 in ICR (CD‐1) mice. Animals were randomly assigned to the following groups: Sham, SCI, SCI + GMSCs (1 × 106 cell/i.v.), SCI + MOR‐GMSCs (1 × 106 cell/i.v.). Our data show that MOR‐treated GMSCs exert anti‐inflammatory and anti‐apoptotic activities. In particular, MOR‐treated GMSCs are able to reduce the spinal cord levels of COX‐2, GFAP, and inflammatory cytokines IL‐1β and IL‐6 and to restore spinal cord normal morphology. Also, MOR‐treated GMSCs influenced the apoptotic pathway, by reducing Bax, caspase 3, and caspase 9 expressions.

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Section: Discussionmentioning

confidence: 99%

Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury

Mammana

Gugliandolo

Cavalli

et al. 2019

J Tissue Eng Regen Med

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“…Indeed, cell replacement therapies provide an opportunity to reconstitute a tissue bridge containing relay neurons (Bonner & Steward, ) by generating a more permissive environment for endogenous axonal sprouting. Recently, different cell therapies have been developed with success in animal models (Ahuja & Fehlings, ; Kjell & Olson, ); however, only a few have been translated into the clinic (Curtis et al, ; Theodore et al, ; Vismara, Papa, Rossi, Forloni, & Veglianese, ). Both adult and neuronal neural progenitor cells offer a suitable niche, comprising neurons and glial cells, compatible with the neural microenvironment, avoiding the undesired potential tumorigenic effect of embryonic tissues (Steward, Sharp, Yee, Hatch, & Bonner, ).…”

Section: Introductionmentioning

confidence: 99%

Biohybrids for spinal cord injury repair

Martínez‐Ramos

Doblado

Mocholi

et al. 2019

J Tissue Eng Regen Med

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Spinal cord injuries (SCIs) result in the loss of sensory and motor function with massive cell death and axon degeneration. We have previously shown that transplantation of spinal cord-derived ependymal progenitor cells (epSPC) significantly improves functional recovery after acute and chronic SCI in experimental models, via neuronal differentiation and trophic glial cell support. Here, we propose an improved procedure based on transplantation of epSPC in a tubular conduit of hyaluronic acid containing poly (lactic acid) fibres creating a biohybrid scaffold. In vitro analysis showed that the poly (lactic acid) fibres included in the conduit induce a preferential neuronal fate of the epSPC rather than glial differentiation, favouring elongation of cellular processes. The safety and efficacy of the biohybrid implantation was evaluated in a complete SCI rat model. The conduits allowed efficient epSPC transfer into the spinal cord, improving the preservation of the neuronal tissue by increasing the presence of neuronal fibres at the injury site and by reducing cavities and cyst formation. The biohybrid-implanted animals presented diminished astrocytic reactivity surrounding the scar area, an increased number of preserved neuronal fibres with a horizontal directional pattern, and enhanced coexpression of the growth cone marker GAP43. The biohybrids offer an improved method for cell transplantation with potential capabilities for neuronal tissue regeneration, opening a promising avenue for cell therapies and SCI treatment.

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“…Despite of the primary mechanical injury, SCI evokes a multifactorial and complex pathophysiological process that is also termed secondary injury [3]. Considering the irreversible property of the primary injury, scientists focus on exploring strategies to reduce secondary injury to adjacent tissues, in order to improve outcome of SCI treatments [4].…”

Section: Introductionmentioning

confidence: 99%

Lycium Barbarum Polysaccharides Alleviates Oxidative Damage Induced by H2O2 Through Down-Regulating MicroRNA-194 in PC-12 and SH-SY5Y Cells

Niu

Jin

Niu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Currently, scientists attempt to improve outcome of spinal cord injury (SCI) via reducing secondary injury during SCI. Oxidative stress is critical for pathophysiology of secondary damage, thus we mainly focused on the anti-oxidant effects of Lycium barbarum polysaccharides (LBPs) on PC-12 and SH-SY5Y cells as well as the underlying mechanisms. Methods: Oxidative stress was induced by H₂O₂ stimulation. Effects of LBPs on cell viability, apoptosis, and expression of proteins associated with apoptosis and autophagy in H₂O₂-induced cells were assessed by CCK-8 assay, flow cytometry assay and Western blot analysis, respectively. Then, expression of miR-194 was determined by qRT-PCR. Expression of miR-194 was dysregulated, and whether LBPs affected H₂O₂-treated cells through modulating miR-194 was verified. The expression of key kinases in the PI3K/AKT pathway and the intracellular levels of ROS and NO were testified by Western blot analysis and flow cytometry with fluorescent probes. Results: H₂O₂-induced decrease of cell viability and increases of apoptosis and autophagy in PC-12 cells were mitigated by LBPs treatment. Next, we found that miR-194 expression was both down-regulated by LBPs treatment in PC-12 and SH-SY5Y cells. More experiments consolidated that influence of LBPs on H₂O₂-treated cells was reversed by miR-194 overexpression while was augmented by miR-194 inhibition. LBPs elevated the phosphorylated levels of PI3K and AKT and reduced levels of ROS and NO through miR-194. Conclusion: LBPs alleviated H₂O₂-induced decrease of cell viability, and increase of apoptosis and autophagy through down-regulating miR-194. Moreover, LBPs activated the PI3K/AKT pathway and reduced oxidative stress through miR-194.

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Current Options for Cell Therapy in Spinal Cord Injury

Cited by 162 publications

References 155 publications

Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury

Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury

Biohybrids for spinal cord injury repair

Lycium Barbarum Polysaccharides Alleviates Oxidative Damage Induced by H2O2 Through Down-Regulating MicroRNA-194 in PC-12 and SH-SY5Y Cells

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