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

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

The transplantation of Wharton's jelly derived mesenchymal stromal cells (WJ-MSCs) possesses therapeutic potential for the treatment of a spinal cord injury (SCI). Generally, the main effect of MSCs is mediated by their paracrine potential. Therefore, application of WJ-MSC derived conditioned media (CM) is an acknowledged approach for how to bypass the limited survival of transplanted cells. In this study, we compared the effect of human WJ-MSCs and their CM in the treatment of SCI in rats. WJ-MSCs and their CM were intrathecally transplanted in the three consecutive weeks following the induction of a balloon compression lesion. Behavioral analyses were carried out up to 9 weeks after the SCI and revealed significant improvement after the treatment with WJ-MSCs and CM, compared to the saline control. Both WJ-MSCs and CM treatment resulted in a higher amount of spared gray and white matter and enhanced expression of genes related to axonal growth. However, only the CM treatment further improved axonal sprouting and reduced the number of reactive astrocytes in the lesion area. On the other hand, WJ-MSCs enhanced the expression of inflammatory and chemotactic markers in plasma, which indicates a systemic immunological response to xenogeneic cell transplantation. Our results confirmed that WJ-MSC derived CM offer an alternative to direct stem cell transplantation for the treatment of SCI.

• Klíčová slova
• Wharton’s jelly, cell secretome, cell therapy, conditioned medium, mesenchymal stem cells, spinal cord injury,
• MeSH
• cytokiny krev   MeSH
• krysa rodu Rattus MeSH
• kultivační média speciální farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• poranění míchy krev   patofyziologie   terapie   MeSH
• potkani Wistar MeSH
• transplantace mezenchymálních kmenových buněk * metody   MeSH
• Whartonův rosol cytologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny MeSH
• kultivační média speciální MeSH

Extracellular matrix (ECM) hydrogels, produced by tissue decellularization are natural injectable materials suitable for neural tissue repair. However, the rapid biodegradation of these materials may disrupt neural tissue reconstruction in vivo. The aim of this study was to improve the stability of the previously described ECM hydrogel derived from human umbilical cord using genipin and N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), crosslinking at concentration of 0.5-10 mM. The hydrogels, crosslinked by genipin (ECM/G) or EDC (ECM/D), were evaluated in vitro in terms of their mechanical properties, degradation stability and biocompatibility. ECM/G, unlike ECM/D, crosslinked hydrogels revealed improved rheological properties when compared to uncrosslinked ECM. Both ECM/G and ECM/D slowed down the gelation time and increased the resistance against in vitro enzymatic degradation, while genipin crosslinking was more effective than EDC. Crosslinkers concentration of 1 mM enhanced the in vitro bio-stability of both ECM/G and ECM/D without affecting mesenchymal stem cell proliferation, axonal sprouting or neural stem cell growth and differentiation. Moreover, when injected into cortical photochemical lesion, genipin allowed in situ gelation and improved the retention of ECM for up to 2 weeks without any adverse tissue response or enhanced inflammatory reaction. In summary, we demonstrated that genipin, rather than EDC, improved the bio-stability of injectable ECM hydrogel in biocompatible concentration, and that ECM/G has potential as a scaffold for neural tissue application.

• MeSH
• extracelulární matrix chemie   MeSH
• hydrogely chemie   MeSH
• iridoidy * MeSH
• karbodiimidy aplikace a dávkování   MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• proliferace buněk fyziologie   MeSH
• pupečník cytologie   MeSH
• regenerace nervu fyziologie   MeSH
• tkáňové inženýrství MeSH
• tkáňové podpůrné struktury chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-ethyl-3-(3-(diethylamino)propyl)carbodiimide MeSH Prohlížeč
• genipin MeSH Prohlížeč
• hydrogely MeSH
• iridoidy * MeSH
• karbodiimidy MeSH

• Publikační typ
• časopisecké články MeSH

A rigorous biochemical analysis of interactions between non-thermal plasmas (NTPs) and living cells has become an important research topic, due to recent developments in biomedical applications of non-thermal plasmas. Here, we decouple distinct cell death pathways targeted by chemically different NTPs. We show that helium NTP cells treatment, results in necrosome formation and necroptosis execution, whereas air NTP leads to mTOR activation and autophagy inhibition, that induces mTOR-related necrosis. On the contrary, ozone (abundant component of air NTP) treatment alone, exhibited the highest levels of reactive oxygen species production leading to CypD-related necrosis via the mitochondrial permeability transition. Our findings offer a novel insight into plasma-induced cellular responses, and reveal distinct cell death pathways triggered by NTPs.

• MeSH
• apoptóza účinky léků   MeSH
• buněčná smrt účinky léků   MeSH
• buněčné linie MeSH
• buňky NIH 3T3 MeSH
• helium chemie   farmakologie   MeSH
• myši MeSH
• nekróza metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• plazmové plyny analýza   chemie   farmakologie   MeSH
• poškození DNA účinky léků   MeSH
• reaktivní formy dusíku metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• helium MeSH
• plazmové plyny MeSH
• reaktivní formy dusíku MeSH
• reaktivní formy kyslíku MeSH