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.

• Keywords
• amyotrophic lateral sclerosis, biomaterials, cell therapy, conditioned medium, exosomes, mesenchymal stem cells, neurodegenerative diseases, spinal cord injury,
• Publication type
• Journal Article MeSH
• Review 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.

• Keywords
• Biomaterials, Cell delivery, Hydrogel, Magnetic field, Spinal cord injury,
• MeSH
• Biocompatible Materials pharmacology   therapeutic use   MeSH
• Hydrogels therapeutic use   MeSH
• Humans MeSH
• Magnetic Field Therapy methods   trends   MeSH
• Spinal Cord Injuries physiopathology   therapy   MeSH
• Nerve Regeneration drug effects   physiology   MeSH
• Stem Cell Transplantation methods   trends   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Hydrogels 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.

• Keywords
• Wharton’s jelly, cell secretome, cell therapy, conditioned medium, mesenchymal stem cells, spinal cord injury,
• MeSH
• Cytokines blood   MeSH
• Rats MeSH
• Culture Media, Conditioned pharmacology   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Mesenchymal Stem Cells cytology   MeSH
• Spinal Cord Injuries blood   physiopathology   therapy   MeSH
• Rats, Wistar MeSH
• Mesenchymal Stem Cell Transplantation * methods   MeSH
• Wharton Jelly cytology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytokines MeSH
• Culture Media, Conditioned 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
• Extracellular Matrix chemistry   MeSH
• Hydrogels chemistry   MeSH
• Iridoids * MeSH
• Carbodiimides administration & dosage   MeSH
• Humans MeSH
• Mesenchymal Stem Cells cytology   MeSH
• Cell Proliferation physiology   MeSH
• Umbilical Cord cytology   MeSH
• Nerve Regeneration physiology   MeSH
• Tissue Engineering MeSH
• Tissue Scaffolds chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 1-ethyl-3-(3-(diethylamino)propyl)carbodiimide MeSH Browser
• genipin MeSH Browser
• Hydrogels MeSH
• Iridoids * MeSH
• Carbodiimides MeSH

• Publication type
• Journal Article 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
• Apoptosis drug effects   MeSH
• Cell Death drug effects   MeSH
• Cell Line MeSH
• NIH 3T3 Cells MeSH
• Helium chemistry   pharmacology   MeSH
• Mice MeSH
• Necrosis metabolism   MeSH
• Oxidative Stress drug effects   MeSH
• Plasma Gases analysis   chemistry   pharmacology   MeSH
• DNA Damage drug effects   MeSH
• Reactive Nitrogen Species metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Spectroscopy, Fourier Transform Infrared MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Helium MeSH
• Plasma Gases MeSH
• Reactive Nitrogen Species MeSH
• Reactive Oxygen Species MeSH