Nejvíce citovaný článek - PubMed ID 29089983
Extracellular matrix based biomaterials for central nervous system tissue repair: the benefits and drawbacks
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
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