Methacrylate hydrogels have been extensively used as bridging scaffolds in experimental spinal cord injury (SCI) research. As synthetic materials, they can be modified, which leads to improved bridging of the lesion. Fibronectin, a glycoprotein of the extracellular matrix produced by reactive astrocytes after SCI, is known to promote cell adhesion. We implanted 3 methacrylate hydrogels: a scaffold based on hydroxypropylmethacrylamid (HPMA), 2-hydroxyethylmethacrylate (HEMA) and a HEMA hydrogel with an attached fibronectin (HEMA-Fn) in an experimental model of acute SCI in rats. The animals underwent functional evaluation once a week and the spinal cords were histologically assessed 3 months after hydrogel implantation. We found that both the HPMA and the HEMA-Fn hydrogel scaffolds lead to partial sensory improvement compared to control animals and animals treated with plain HEMA scaffold. The HPMA scaffold showed an increased connective tissue infiltration compared to plain HEMA hydrogels. There was a tendency towards connective tissue infiltration and higher blood vessel ingrowth in the HEMA-Fn scaffold. HPMA hydrogels showed a significantly increased axonal ingrowth compared to HEMA-Fn and plain HEMA; while there were some neurofilaments in the peripheral as well as the central region of the HEMA-Fn scaffold, no neurofilaments were found in plain HEMA hydrogels. In conclusion, HPMA hydrogel as well as the HEMA-Fn scaffold showed better bridging qualities compared to the plain HEMA hydrogel, which resulted in very limited partial sensory improvement.
- Klíčová slova
- connective tissue, hydrogel, locomotor test, neurofilaments, plantar test, spinal cord injury,
- MeSH
- axony fyziologie MeSH
- biokompatibilní materiály MeSH
- biologické markery MeSH
- exprese genu MeSH
- extracelulární matrix metabolismus MeSH
- fyziologická neovaskularizace MeSH
- hematoencefalická bariéra metabolismus MeSH
- hojení ran MeSH
- hydrogely * MeSH
- krysa rodu Rattus MeSH
- methakryláty * chemie MeSH
- modely nemocí na zvířatech MeSH
- pojivová tkáň MeSH
- poranění míchy etiologie metabolismus patologie terapie MeSH
- regenerace nervu * MeSH
- tkáňové podpůrné struktury MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- biologické markery MeSH
- hydrogely * MeSH
- methakryláty * MeSH
Human mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis. Endogenous gene expression (Gfap, Casp3, Irf5, Cd86, Mrc1, Cd163) was studied with quantitative Real-time polymerase chain reaction (qRT PCR). Significant recovery of functional outcome was observed in all of the treated groups except for the single application of the lowest number of cells. Histochemical analyses revealed a gradually increasing effect of grafted cells, resulting in a significant increase in the number of GAP43+ fibers, a higher amount of spared gray matter and reduced astrogliosis. mRNA expression of macrophage markers and apoptosis was downregulated after the repeated application of 1.5 million cells. We conclude that the effect of hWJ-MSCs on spinal cord regeneration is dose-dependent and potentiated by repeated application.
- Klíčová slova
- Wharton’s jelly, astrogliosis, axonal growth, human mesenchymal stem cells, inflammatory response, neuroregeneration, spinal cord injury,
- MeSH
- apoptóza MeSH
- astrocyty MeSH
- axony metabolismus MeSH
- bílá hmota metabolismus patologie MeSH
- biologické markery MeSH
- buněčná diferenciace MeSH
- exprese genu MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- lidé MeSH
- lokomoce MeSH
- mezenchymální kmenové buňky cytologie metabolismus MeSH
- modely nemocí na zvířatech MeSH
- poranění míchy diagnóza etiologie metabolismus terapie MeSH
- šedá hmota metabolismus patologie MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- viabilita buněk MeSH
- Whartonův rosol cytologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
STUDY DESIGN: A prospective study. OBJECTIVES: Analysis of epidemiological data about acute spinal cord injury (SCI) in the Czech Republic over a period of 10 years (2006-2015). METHODS: A data collection system was implemented in the rehabilitation centres which provides care to patients with acute SCI in the Czech Republic. The recorded variables are as follows: age at time of SCI; gender; cause of injury; neurological level of injury (NLI); and its severity (ASIA Impairment Scale (AIS)). Data from 2006 to 2015 were analysed and trends were determined. RESULTS: The overall number of acute SCI ranges between 250 and 300 cases annually. Two-third of the affected population are males. The average age at time of SCI is 49.1 years. The average incidence of traumatic SCI is 15.5 cases per year and is gradually decreasing. The leading cause of SCI are falls (44.5%), followed by traffic accidents (28.2%) and sports injuries including diving into water (19.7%). The incidence of non-traumatic SCI is 8.6 cases per year on average and has an upward trend. Inflammatory lesions account for 26.7% of cases, tumours account for 20.9%, and vascular related injuries make up 17.7%. The NLI occurs most often in the cervical segments (45.3%). The most frequently occurring lesions are motor incomplete: AIS D (33.3%). CONCLUSION: This study shows a stable occurrence of SCI in the Czech Republic, with cervical and motor incomplete cases being the leading ones. Epidemiological data are needed to improve the care of SCI patients and to promote an active life following it.
- MeSH
- akutní nemoc MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- poranění míchy epidemiologie etiologie MeSH
- prospektivní studie MeSH
- sexuální faktory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Despite advances in our understanding and research of induced pluripotent stem cells (iPSCs), their use in clinical practice is still limited due to lack of preclinical experiments. Neural precursors (NPs) derived from a clone of human iPSCs (IMR90) were used to treat a rat spinal cord lesion 1 week after induction. Functional recovery was evaluated using the BBB, beam walking, rotarod, and plantar tests. Lesion morphology, endogenous axonal sprouting, graft survival, and iPSC-NP differentiation were analyzed immunohistochemically. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted iPSC-NPs on endogenous regenerative processes and also to monitor their behavior after transplantation. Human iPSC-NPs robustly survived in the lesion, migrated, and partially filled the lesion cavity during the entire period of observation. Transplanted animals displayed significant motor improvement already from the second week after the transplantation of iPSC-NPs. qPCR revealed the increased expression of human neurotrophins 8 weeks after transplantation. Simultaneously, the white and gray matter were spared in the host tissue. The grafted cells were immunohistochemically positive for doublecortin, MAP2, βIII-tubulin, GFAP, and CNPase 8 weeks after transplantation. Human iPSC-NPs further matured, and 17 weeks after transplantation differentiated toward interneurons, dopaminergic neurons, serotoninergic neurons, and ChAT-positive motoneurons. Human iPSC-NPs possess neurotrophic properties that are associated with significant early functional improvement and the sparing of spinal cord tissue. Their ability to differentiate into tissue-specific neurons leads to the long-term restoration of the lesioned tissue, making the cells a promising candidate for future cell-based therapy of SCI.
- MeSH
- 2',3'-cyklické nukleotidfosfodiesterasy genetika metabolismus MeSH
- buněčná diferenciace MeSH
- chování zvířat MeSH
- gliový fibrilární kyselý protein genetika metabolismus MeSH
- hematoencefalická bariéra metabolismus MeSH
- indukované pluripotentní kmenové buňky cytologie metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- nervové kmenové buňky cytologie transplantace MeSH
- neurotrofní faktory genetika metabolismus MeSH
- pohyb buněk MeSH
- pohybová aktivita MeSH
- poranění míchy etiologie terapie MeSH
- potkani Wistar MeSH
- protein doublecortin MeSH
- proteiny asociované s mikrotubuly genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- transplantace heterologní MeSH
- tubulin genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2',3'-cyklické nukleotidfosfodiesterasy MeSH
- Dcx protein, rat MeSH Prohlížeč
- gliový fibrilární kyselý protein MeSH
- MAP2 protein, human MeSH Prohlížeč
- neurotrofní faktory MeSH
- protein doublecortin MeSH
- proteiny asociované s mikrotubuly MeSH
- transkripční faktory MeSH
- tubulin MeSH
A case of penetrating spinal cord injury in 47 year old man, caused by migration of Kirschner wire is presented. The patient underwent the operation for acromioclavicular luxation 2 years ago--osteosynthesis with the use of 2 Kirschner wires. Admission with clinical symptoms of severe paraparesis of lower limbs. CT proved penetration of the first K-wire transversally through spinal cord in the level C7/T1, the second one stopped in the right transversal foramen T4. Emergent operation--extraction of Kirschner wires, followed by methyl-prednisolon therapy, according NASCIS II study. Gradual partial recovery of neurological deficit, with ability to walk and continence. Permanent sexual dysfunction.
- MeSH
- akromioklavikulární kloub chirurgie MeSH
- dislokace kloubu chirurgie MeSH
- klíční kost chirurgie MeSH
- kostní dráty škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- migrace cizích těles komplikace MeSH
- ortopedické fixační pomůcky škodlivé účinky MeSH
- penetrující rány etiologie MeSH
- poranění míchy etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The authors present the results of five years' research concerned with experimental injuries of the spinal cord. The authors studied in cats and rabbits four types of problems: 1. the dynamics of injuries of the spinal cord from the morphological and biochemical aspect, in particular the development and shape of the lesion after complete severing of the spinal cord at the L2 level which was performed by 10-second extradural compression of the spinal cord with an artery forceps. 2. The possibility of resection of the destroyed spinal tissue one week after the insult and the development of autodestructive processes after this resection. 3. Resection of the entire vertebra L2 in healthy animals and shortening of the spine by means of an original stabilization apparatus. 4. Resection of the vertebra, resection of the autodestroyed parts of the spinal cord and approximation of the stumps of the spinal cord by shortening the spine. The assembled findings are discussed in conjunction with contemporary research into the reconstruction of spinal functions and possible transplantations of the CNS.
Five patients showed delayed spinal cord damage following high-tension electrical injury. Early specialist care of this complication is necessary and is best carried out in burn units. Our experience shows that recovery may be complete or only partial.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurologické vyšetření MeSH
- paralýza etiologie MeSH
- popálení elektrickým proudem komplikace MeSH
- poranění míchy etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- poranění míchy etiologie patologie MeSH
- Rana esculenta MeSH
- synapse patologie ultrastruktura MeSH
- terapeutická hypotermie * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- box * MeSH
- dospělí MeSH
- lidé MeSH
- neurologické vyšetření MeSH
- poranění míchy etiologie MeSH
- prognóza MeSH
- sportovní úrazy * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
