Regulatory mechanisms of stem cell differentiation: Biotechnological applications for neurogenesis.

The world population's life expectancy is growing, and neurodegenerative disorders common in old age require more efficient therapies. In this context, neural stem cells (NSCs) are imperative for the development and maintenance of the functioning of the nervous system and have broad therapeutic applicability for neurodegenerative diseases. Therefore, knowing all the mechanisms that govern the self-renewal, differentiation, and cell signaling of NSC is necessary. This review will address some of these aspects, including the role of growth and transcription factors, epigenetic modulators, microRNAs, and extracellular matrix components. Furthermore, differentiation and transdifferentiation processes will be addressed as therapeutic strategies showing their significance for stem cell-based therapy.

Strategic use of organoids and organs-on-chip as biomimetic tools.

Organoid development and organ-on-a-chip are technologies based on differentiating stem cells, forming 3D multicellular structures resembling organs and tissues in vivo. Hence, both can be strategically used for disease modeling, drug screening, and host-pathogen studies. In this context, this review highlights the significant advancements in the area, providing technical approaches to organoids and organ-on-a-chip that best imitate in vivo physiology.

Drugs and Endogenous Factors as Protagonists in Neurogenic Stimulation.

Neurogenesis is a biological process characterized by new neurons formation from stem cells. For decades, it was believed that neurons only multiplied during development and in the postnatal period but the discovery of neural stem cells (NSCs) in mature brain promoted a revolution in neuroscience field. In mammals, neurogenesis consists of migration, differentiation, maturation, as well as functional integration of newborn cells into the pre-existing neuronal circuit. Actually, NSC density drops significantly after the first stages of development, however in specific places in the brain, called neurogenic niches, some of these cells retain their ability to generate new neurons and glial cells in adulthood. The subgranular (SGZ), and the subventricular zones (SVZ) are examples of regions where the neurogenesis process occurs in the mature brain. There, the potential of NSCs to produce new neurons has been explored by new advanced methodologies and in neuroscience for the treatment of brain damage and/or degeneration. Based on that, this review highlights endogenous factors and drugs capable of stimulating neurogenesis, as well as the perspectives for the use of NSCs for neurological and neurodegenerative diseases.

The role of neurogenesis in neurorepair after ischemic stroke.

Stroke consists of an abrupt reduction of cerebral blood flow resulting in hypoxia that triggers an excitotoxicity, oxidative stress, and neuroinflammation. After the ischemic process, neural precursor cells present in the subventricular zone of the lateral ventricle and subgranular zone of the dentate gyrus proliferate and migrate towards the lesion, contributing to the brain repair. The neurogenesis is induced by signal transduction pathways, growth factors, attractive factors for neuroblasts, transcription factors, pro and anti-inflammatory mediators and specific neurotransmissions. However, this endogenous neurogenesis occurs slowly and does not allow a complete restoration of brain function. Despite that, understanding the mechanisms of neurogenesis could improve the therapeutic strategies for brain repair. This review presents the current knowledge about brain repair process after stroke and the perspectives regarding the development of promising therapies that aim to improve neurogenesis and its potential to form new neural networks.