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

Axon regeneration in the CNS is inhibited by many extrinsic and intrinsic factors. Because these act in parallel, no single intervention has been sufficient to enable full regeneration of damaged axons in the adult mammalian CNS. In the external environment, NogoA and CSPGs are strongly inhibitory to the regeneration of adult axons. CNS neurons lose intrinsic regenerative ability as they mature: embryonic but not mature neurons can grow axons for long distances when transplanted into the adult CNS, and regeneration fails with maturity in in vitro axotomy models. The causes of this loss of regeneration include partitioning of neurons into axonal and dendritic fields with many growth-related molecules directed specifically to dendrites and excluded from axons, changes in axonal signalling due to changes in expression and localization of receptors and their ligands, changes in local translation of proteins in axons, and changes in cytoskeletal dynamics after injury. Also with neuronal maturation come epigenetic changes in neurons, with many of the transcription factor binding sites that drive axon growth-related genes becoming inaccessible. The overall aim for successful regeneration is to ensure that the right molecules are expressed after axotomy and to arrange for them to be transported to the right place in the neuron, including the damaged axon tip.

• Klíčová slova
• Axon regeneration, Axonal transport, Chondroitin sulphate proteoglycans, Chondroitinase, Epigenetics, Integrins, NogoA, PTEN, Rabs, RhoA, Schwann cell, Signalling, Trafficking,
• MeSH
• axonální transport fyziologie   MeSH
• axony fyziologie   MeSH
• centrální nervový systém cytologie   fyziologie   MeSH
• lidé MeSH
• nervový útlum fyziologie   MeSH
• neurogeneze fyziologie   MeSH
• proteosyntéza fyziologie   MeSH
• regenerace nervu fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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

PURPOSE: Vertebral body defects represent one of the most common orthopedic challenges. In order to advance the transfer of stem cell therapies into orthopedic clinical practice, we performed this study to evaluate the safety and efficacy of a composite bioartificial graft based on a hydroxyapatite bone scaffold (CEM-OSTETIC(®)) combined with human mesenchymal stem cells (MSCs) in a rat model of vertebral body defects. METHODS: Under general isoflurane anesthesia, a defect in the body of the L2 vertebra was prepared and left to heal spontaneously (group 1), implanted with scaffold material alone (group 2), or implanted with a scaffold together with 0.5 million MSCs (group 3) or 5 million MSCs (group 4). The rats were killed 8 weeks after surgery. Histological and histomorphometrical evaluation of the implant as well as micro-CT imaging of the vertebrae were performed. RESULTS: We observed a significant effect on the formation of new bone tissue in the defect in group 4 when compared to the other groups and a reduced inflammatory reaction in both groups receiving a scaffold and MSCs. We did not detect any substantial pathological changes or tumor formation after graft implantation. CONCLUSIONS: MSCs in combination with a hydroxyapatite scaffold improved the repair of a model bone defect and might represent a safe and effective alternative in the treatment of vertebral bone defects.

• MeSH
• bederní obratle diagnostické zobrazování   zranění   patologie   MeSH
• hojení ran MeSH
• hydroxyapatit * MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• poranění páteře diagnostické zobrazování   patologie   terapie   MeSH
• potkani Wistar MeSH
• radiografie MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury * MeSH
• transplantace kostí metody   MeSH
• transplantace mezenchymálních kmenových buněk metody   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
• hydroxyapatit * MeSH

BACKGROUND: A number of cardiovascular, neurological, musculoskeletal and other diseases have a limited capacity for repair and only a modest progress has been made in treatment of brain diseases. The discovery of stem cells has opened new possibilities for the treatment of these maladies, and cell therapy now stands at the cutting-edge of modern regenerative medicine and tissue engineering. Experimental data and the first clinical trials employing stem cells have shown their broad therapeutic potential and have brought hope to patients suffering from devastating pathologies of different organs and systems. AIMS: Here, we briefly review the main achievements and trends in cell-based therapy, with an emphasis on the main types of stem cells: embryonic, mesenchymal stromal and induced pluripotent cells. DISCUSSION: Many questions regarding the application of stem cells remain unanswered, particularly tumorigenicity, immune rejection and danger of gene manipulation. Currently, only MSC seems to be safe and might be considered to be a leading candidate for human application to treat pathologies that affect the cardiovascular, neurological and musculoskeletal systems.

• Klíčová slova
• Clinical Trials, Embryonic Stem Cells, Induced Pluripotent Stem Cells, Mesenchymal Stromal Cells, PACS: 87.19.L-; 87.19.LW, Stem Cells,
• Publikační typ
• časopisecké články MeSH

The transplantation of mesenchymal stem cells (MSC) is currently under study as a therapeutic approach for spinal cord injury, and the number of transplanted cells that reach the lesioned tissue is one of the critical parameters. In this study, intrathecally transplanted cells labeled with superparamagnetic iron oxide nanoparticles were guided by a magnetic field and successfully targeted near the lesion site in the rat spinal cord. Magnetic resonance imaging and histological analysis revealed significant differences in cell numbers and cell distribution near the lesion site under the magnet in comparison to control groups. The cell distribution correlated well with the calculated distribution of magnetic forces exerted on the transplanted cells in the subarachnoid space and lesion site. The kinetics of the cells' accumulation near the lesion site is described within the framework of a mathematical model that reveals those parameters critical for cell targeting and suggests ways to enhance the efficiency of magnetic cell delivery. In particular, we show that the targeting efficiency can be increased by using magnets that produce spatially modulated stray fields. Such magnetic systems with tunable geometric parameters may provide the additional level of control needed to enhance the efficiency of stem cell delivery in spinal cord injury.

• Klíčová slova
• magnetism, mesenchymal stem cell, modeling, nanoparticle, spinal cord injury,
• MeSH
• histocytochemie MeSH
• krysa rodu Rattus MeSH
• magnetické nanočástice aplikace a dávkování   chemie   terapeutické užití   MeSH
• magnety * MeSH
• mezenchymální kmenové buňky chemie   cytologie   MeSH
• mícha chemie   cytologie   MeSH
• poranění míchy chirurgie   MeSH
• potkani Sprague-Dawley MeSH
• spinální injekce MeSH
• teoretické modely MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• magnetické nanočástice MeSH