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
The burden of neurodegenerative disorders in an aging population has become a challenge for the modern world. While the biomarkers available and the methods of diagnosis have improved to detect the onset of these diseases at early stages, the question of adapted and efficient therapies is still a major issue. The prospect of replacing the loss of functional neural cells remains an attractive but still audacious approach. A huge progress has been made in the generation of neurons derived from human stem cell lines and transplantation assays are tested in animals for a wide range of pathologies of the central nervous system. Here we take one step back and examine neuronal differentiation and the characterization of neural progenitors derived from human embryonic stem cells. We gather results from our previous studies and present a cell model that was successfully used in functional analyses and engraftment experiments. These neuronal precursors exhibit spontaneous and evoked activity, indicating that their electrophysiological and calcium handling properties are similar to those of matured neurons. Hence this summarized information will serve as a basis to design better stem cell-based therapies to improve neural regeneration.
- Klíčová slova
- calcium signaling, human embryonic stem cell, immortalized stem cell lines, ion channels, neural precursors, neurodegenerative diseases, spinal cord,
- Publikační typ
- časopisecké články MeSH