Preclinical and clinical studies with various stem cells, their secretomes, and extracellular vesicles (EVs) indicate their use as a promising strategy for the treatment of various diseases and tissue defects, including neurodegenerative diseases such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Autologous and allogenic mesenchymal stem cells (MSCs) are so far the best candidates for use in regenerative medicine. Here we review the effects of the implantation of MSCs (progenitors of mesodermal origin) in animal models of SCI and ALS and in clinical studies. MSCs possess multilineage differentiation potential and are easily expandable in vitro. These cells, obtained from bone marrow (BM), adipose tissue, Wharton jelly, or even other tissues, have immunomodulatory and paracrine potential, releasing a number of cytokines and factors which inhibit the proliferation of T cells, B cells, and natural killer cells and modify dendritic cell activity. They are hypoimmunogenic, migrate toward lesion sites, induce better regeneration, preserve perineuronal nets, and stimulate neural plasticity. There is a wide use of MSC systemic application or MSCs seeded on scaffolds and tissue bridges made from various synthetic and natural biomaterials, including human decellularized extracellular matrix (ECM) or nanofibers. The positive effects of MSC implantation have been recorded in animals with SCI lesions and ALS. Moreover, promising effects of autologous as well as allogenic MSCs for the treatment of SCI and ALS were demonstrated in recent clinical studies.

• Klíčová slova
• amyotrophic lateral sclerosis, biomaterials, cell therapy, conditioned medium, exosomes, mesenchymal stem cells, neurodegenerative diseases, spinal cord injury,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) treatment is stem cell therapy. Neural progenitors derived from induced pluripotent cells (NP-iPS) might rescue or replace dying motoneurons (MNs). However, the mechanisms responsible for the beneficial effect are not fully understood. The aim here was to investigate the mechanism by studying the effect of intraspinally injected NP-iPS into asymptomatic and early symptomatic superoxide dismutase (SOD)1G93A transgenic rats. Prior to transplantation, NP-iPS were characterized in vitro for their ability to differentiate into a neuronal phenotype. Motor functions were tested in all animals, and the tissue was analyzed by immunohistochemistry, qPCR, and Western blot. NP-iPS transplantation significantly preserved MNs, slowed disease progression, and extended the survival of all treated animals. The dysregulation of spinal chondroitin sulfate proteoglycans was observed in SOD1G93A rats at the terminal stage. NP-iPS application led to normalized host genes expression (versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3) and the protection of perineuronal nets around the preserved MNs. In the host spinal cord, transplanted cells remained as progenitors, many in contact with MNs, but they did not differentiate. The findings suggest that NP-iPS demonstrate neuroprotective properties by regulating local gene expression and regulate plasticity by modulating the central nervous system (CNS) extracellular matrix such as perineuronal nets (PNNs).

• Klíčová slova
• ALS, iPS, motoneuron death, neurodegeneration, plasticity, proteoglycans, stem cells, transplantation,
• MeSH
• amyotrofická laterální skleróza terapie   MeSH
• indukované pluripotentní kmenové buňky cytologie   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• nervové kmenové buňky cytologie   metabolismus   transplantace   MeSH
• neuroplasticita * MeSH
• neurotrofní faktory genetika   metabolismus   MeSH
• periferní nervy fyziologie   MeSH
• potkani Sprague-Dawley MeSH
• proteiny regulující apoptózu genetika   metabolismus   MeSH
• regenerace nervu MeSH
• tenascin genetika   metabolismus   MeSH
• transplantace kmenových buněk metody   MeSH
• versikany genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• neurotrofní faktory MeSH
• proteiny regulující apoptózu MeSH
• tenascin MeSH
• versikany MeSH

Spinal cord injury (SCI), is a devastating condition leading to the loss of locomotor and sensory function below the injured segment. Despite some progress in acute SCI treatment using stem cells and biomaterials, chronic SCI remains to be addressed. We have assessed the use of laminin-coated hydrogel with dual porosity, seeded with induced pluripotent stem cell-derived neural progenitors (iPSC-NPs), in a rat model of chronic SCI. iPSC-NPs cultured for 3 weeks in hydrogel in vitro were positive for nestin, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2). These cell-polymer constructs were implanted into a balloon compression lesion, 5 weeks after lesion induction. Animals were behaviorally tested, and spinal cord tissue was immunohistochemically analyzed 28 weeks after SCI. The implanted iPSC-NPs survived in the scaffold for the entire experimental period. Host axons, astrocytes and blood vessels grew into the implant and an increased sprouting of host TH+ fibers was observed in the lesion vicinity. The implantation of iPSC-NP-LHM cell-polymer construct into the chronic SCI led to the integration of material into the injured spinal cord, reduced cavitation and supported the iPSC-NPs survival, but did not result in a statistically significant improvement of locomotor recovery.

• Klíčová slova
• Chronic spinal cord injury, HEMA hydrogel, human induced pluripotent stem cells, laminin, neural progenitors, surface charge,
• MeSH
• buněčná diferenciace MeSH
• chronická nemoc MeSH
• hydrogely MeSH
• indukované pluripotentní kmenové buňky metabolismus   MeSH
• krysa rodu Rattus MeSH
• nervové kmenové buňky transplantace   MeSH
• poranění míchy terapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hydrogely 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

Dental stem cells are an emerging star on a stage that is already quite populated. Recently, there has been a lot of hype concerning these cells in dental therapies, especially in regenerative endodontics. It is fitting that most research is concentrated on dental regeneration, although other uses for these cells need to be explored in more detail. Being a true mesenchymal stem cell, their capacities could also prove beneficial in areas outside their natural environment. One such field is the central nervous system, and in particular, repairing the injured spinal cord. One of the most formidable challenges in regenerative medicine is to restore function to the injured spinal cord, and as yet, a cure for paralysis remains to be discovered. A variety of approaches have already been tested, with graft-based strategies utilising cells harbouring appropriate properties for neural regeneration showing encouraging results. Here we present a review focusing on properties of dental stem cells that endorse their use in regenerative medicine, with particular emphasis on repairing the damaged spinal cord.

• Klíčová slova
• Dental stem cells, Growth factors, Immunomodulation, Neuroprotection, Spinal cord injury,
• MeSH
• kmenové buňky cytologie   MeSH
• lidé MeSH
• neurotrofní faktory metabolismus   MeSH
• poranění míchy terapie   MeSH
• receptory faktorů růstu nervů metabolismus   MeSH
• regenerativní lékařství MeSH
• transplantace kmenových buněk * MeSH
• zubní dřeň cytologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• neurotrofní faktory MeSH
• receptory faktorů růstu nervů MeSH

BACKGROUND: Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration. METHODS: In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR. RESULTS: Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2 months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction. CONCLUSIONS: Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration.

• MeSH
• buněčná diferenciace MeSH
• indukované pluripotentní kmenové buňky cytologie   transplantace   MeSH
• krysa rodu Rattus MeSH
• lokomoce MeSH
• nervové kmenové buňky cytologie   transplantace   MeSH
• parakrinní signalizace MeSH
• poranění míchy patologie   patofyziologie   terapie   MeSH
• potkani Wistar MeSH
• proteiny nervové tkáně genetika   metabolismus   MeSH
• regenerace nervu MeSH
• spinální injekce metody   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• proteiny nervové tkáně MeSH