Spinal cord injury (SCI) is a serious trauma, which often results in a permanent loss of motor and sensory functions, pain and spasticity. Despite extensive research, there is currently no available therapy that would restore the lost functions after SCI in human patients. Advanced treatments use regenerative medicine or its combination with various interdisciplinary approaches such as tissue engineering or biophysical methods. This review summarizes and critically discusses the research from specific interdisciplinary fields in SCI treatment such as the development of biomaterials as scaffolds for tissue repair, and using a magnetic field for targeted cell delivery. We compare the treatment effects of synthetic non-degradable methacrylate-based hydrogels and biodegradable biological scaffolds based on extracellular matrix. The systems using magnetic fields for magnetically guided delivery of stem cells loaded with magnetic nanoparticles into the lesion site are then suggested and discussed.

• Keywords
• Biomaterials, Cell delivery, Hydrogel, Magnetic field, Spinal cord injury,
• MeSH
• Biocompatible Materials pharmacology   therapeutic use   MeSH
• Hydrogels therapeutic use   MeSH
• Humans MeSH
• Magnetic Field Therapy methods   trends   MeSH
• Spinal Cord Injuries physiopathology   therapy   MeSH
• Nerve Regeneration drug effects   physiology   MeSH
• Stem Cell Transplantation methods   trends   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Hydrogels MeSH

INTRODUCTION: Rat mesenchymal stem cells (rMSCs) labeled with 1) poly-l-lysine-coated superparamagnetic iron oxide nanoparticles or 2) silica-coated cobalt-zinc-iron nanoparticles were implanted into the left brain hemisphere of rats, to assess their effects on the levels of oxidative damage to biological macromolecules in brain tissue. METHODS: Controls were implanted with unlabeled rMSCs. Animals were sacrificed 24 hours or 4 weeks after the treatment, and the implantation site along with the surrounding tissue was isolated from the brain. At the same intervals, parallel groups of animals were scanned in vivo by magnetic resonance imaging (MRI). The comet assay with enzymes of excision DNA repair (endonuclease III and formamidopyrimidine-DNA glycosylase) was used to analyze breaks and oxidative damage to DNA in the brain tissue. Oxidative damage to proteins and lipids was determined by measuring the levels of carbonyl groups and 15-F2t-isoprostane (enzyme-linked immunosorbent assay). MRI displayed implants of labeled cells as extensive hypointense areas in the brain tissue. In histological sections, the expression of glial fibrillary acidic protein and CD68 was analyzed to detect astrogliosis and inflammatory response. RESULTS: Both contrast labels caused a similar response in the T2-weighted magnetic resonance (MR) image and the signal was clearly visible within 4 weeks after implantation of rMSCs. No increase of oxidative damage to DNA, lipids, or proteins over the control values was detected in any sample of brain tissue from the treated animals. Also, immunohistochemistry did not indicate any serious tissue impairment around the graft. CONCLUSION: Both tested types of nanoparticles appear to be prospective and safe labels for tracking the transplanted cells by MR.

• Keywords
• MRI, cell transplantation, comet assay, genotoxicity, lipid peroxidation, protein oxidative damage,
• MeSH
• Dinoprost analogs & derivatives   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Isoprostanes analysis   metabolism   MeSH
• Cobalt chemistry   MeSH
• Metal Nanoparticles administration & dosage   chemistry   toxicity   MeSH
• Magnetic Resonance Imaging methods   MeSH
• Mesenchymal Stem Cells chemistry   MeSH
• Brain diagnostic imaging   drug effects   metabolism   MeSH
• Silicon Dioxide chemistry   MeSH
• Rats, Inbred Lew MeSH
• Prospective Studies MeSH
• Tissue Extracts MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Ferric Compounds chemistry   MeSH
• Iron chemistry   MeSH
• Zinc chemistry   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 8-epi-prostaglandin F2alpha MeSH Browser
• Dinoprost MeSH
• ferric oxide MeSH Browser
• Isoprostanes MeSH
• Cobalt MeSH
• Silicon Dioxide MeSH
• Tissue Extracts MeSH
• Ferric Compounds MeSH
• Iron MeSH
• Zinc MeSH

Spinal cord injury (SCI) is a devastating condition that usually results in sudden and long-lasting locomotor and sensory neuron degeneration below the lesion site. During the last two decades, the search for new therapies has been revolutionized with the improved knowledge of stem cell (SC) biology. SCs therapy offers several attractive strategies for spinal cord repair. The transplantation of SCs promotes remyelination, neurite outgrowth and axonal elongation, and activates resident or transplanted progenitor cells across the lesion cavity. However, optimized growth and differentiation protocols along with reliable safety assays should be established prior to the clinical application of SCs. Additionally, the ideal method of SCs labeling for efficient cell tracking after SCI remains a challenging issue that requires further investigation. This review summarizes the current findings on the SCs-based therapeutic strategies, and compares different SCs labeling approaches for SCI.

• Keywords
• spinal cord injury, stem cell labeling, stem cells,
• MeSH
• Cell Tracking methods   MeSH
• Humans MeSH
• Neural Stem Cells cytology   transplantation   MeSH
• Neurogenesis MeSH
• Spinal Cord Injuries diagnostic imaging   pathology   therapy   MeSH
• Nerve Regeneration MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

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.

• MeSH
• Chemokine CCL5 genetics   metabolism   MeSH
• Fibroblast Growth Factor 2 genetics   metabolism   MeSH
• Glial Fibrillary Acidic Protein genetics   metabolism   MeSH
• Interferon Regulatory Factors genetics   metabolism   MeSH
• Interleukins genetics   metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Locomotion MeSH
• Mesenchymal Stem Cells metabolism   MeSH
• Spinal Cord Injuries metabolism   therapy   MeSH
• Rats, Wistar MeSH
• GAP-43 Protein genetics   metabolism   MeSH
• Receptors, Immunologic genetics   metabolism   MeSH
• Tumor Necrosis Factor-alpha genetics   metabolism   MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chemokine CCL5 MeSH
• Fibroblast Growth Factor 2 MeSH
• Glial Fibrillary Acidic Protein MeSH
• Interferon Regulatory Factors MeSH
• Interleukins MeSH
• GAP-43 Protein MeSH
• Receptors, Immunologic MeSH
• Tumor Necrosis Factor-alpha MeSH