Nejvíce citovaný článek - PubMed ID 22888231
Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury
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.
- Klíčová slova
- Biomaterials, Cell delivery, Hydrogel, Magnetic field, Spinal cord injury,
- MeSH
- biokompatibilní materiály farmakologie terapeutické užití MeSH
- hydrogely terapeutické užití MeSH
- lidé MeSH
- magnetoterapie metody trendy MeSH
- poranění míchy patofyziologie terapie MeSH
- regenerace nervu účinky léků fyziologie MeSH
- transplantace kmenových buněk metody trendy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- hydrogely 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.
- Klíčová slova
- MRI, cell transplantation, comet assay, genotoxicity, lipid peroxidation, protein oxidative damage,
- MeSH
- dinoprost analogy a deriváty MeSH
- ELISA MeSH
- isoprostany analýza metabolismus MeSH
- kobalt chemie MeSH
- kovové nanočástice aplikace a dávkování chemie toxicita MeSH
- magnetická rezonanční tomografie metody MeSH
- mezenchymální kmenové buňky chemie MeSH
- mozek diagnostické zobrazování účinky léků metabolismus MeSH
- oxid křemičitý chemie MeSH
- potkani inbrední LEW MeSH
- prospektivní studie MeSH
- tkáňové extrakty MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- železité sloučeniny chemie MeSH
- železo chemie MeSH
- zinek chemie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 8-epi-prostaglandin F2alpha MeSH Prohlížeč
- dinoprost MeSH
- ferric oxide MeSH Prohlížeč
- isoprostany MeSH
- kobalt MeSH
- oxid křemičitý MeSH
- tkáňové extrakty MeSH
- železité sloučeniny MeSH
- železo MeSH
- zinek 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.
- Klíčová slova
- spinal cord injury, stem cell labeling, stem cells,
- MeSH
- buněčný tracking metody MeSH
- lidé MeSH
- nervové kmenové buňky cytologie transplantace MeSH
- neurogeneze MeSH
- poranění míchy diagnostické zobrazování patologie terapie MeSH
- regenerace nervu MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy 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
- chemokin CCL5 genetika metabolismus MeSH
- fibroblastový růstový faktor 2 genetika metabolismus MeSH
- gliový fibrilární kyselý protein genetika metabolismus MeSH
- interferonové regulační faktory genetika metabolismus MeSH
- interleukiny genetika metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- lokomoce MeSH
- mezenchymální kmenové buňky metabolismus MeSH
- poranění míchy metabolismus terapie MeSH
- potkani Wistar MeSH
- protein GAP-43 genetika metabolismus MeSH
- receptory imunologické genetika metabolismus MeSH
- TNF-alfa genetika metabolismus MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemokin CCL5 MeSH
- fibroblastový růstový faktor 2 MeSH
- gliový fibrilární kyselý protein MeSH
- interferonové regulační faktory MeSH
- interleukiny MeSH
- protein GAP-43 MeSH
- receptory imunologické MeSH
- TNF-alfa MeSH