Directional induction of neural stem cells, a new therapy for neurodegenerative diseases and ischemic stroke

Abstract

Due to the limited capacity of the adult mammalian brain to self-repair and regenerate, neurological diseases, especially neurodegenerative disorders and stroke, characterized by irreversible cellular damage are often considered as refractory diseases. Neural stem cells (NSCs) play a unique role in the treatment of neurological diseases for their abilities to self-renew and form different neural lineage cells, such as neurons and glial cells. With the increasing understanding of neurodevelopment and advances in stem cell technology, NSCs can be obtained from different sources and directed to differentiate into a specific neural lineage cell phenotype purposefully, making it possible to replace specific cells lost in some neurological diseases, which provides new approaches to treat neurodegenerative diseases as well as stroke. In this review, we outline the advances in generating several neuronal lineage subtypes from different sources of NSCs. We further summarize the therapeutic effects and possible therapeutic mechanisms of these fated specific NSCs in neurological disease models, with special emphasis on Parkinson’s disease and ischemic stroke. Finally, from the perspective of clinical translation, we compare the strengths and weaknesses of different sources of NSCs and different methods of directed differentiation, and propose future research directions for directed differentiation of NSCs in regenerative medicine.

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

“…The lack of use of NSC‐derived sEVs in clinical trials might be partially because of the constrained supply of their parental cells. [ 201 ] Luckily, recent studies have developed fibroblast‐derived iNSCs, opening a new window for obtaining sEVs from NSC‐like cells. These iNSC‐sEV could not only promote cell survival and proliferation no less than NSC‐sEV in vitro, [ 202 ] but also enhance recovery after ischemic stroke [ 105b ] and mitigate AD‐like phenotypes in preclinical models.…”

Huntington’s Disease: Complex Pathogenesis and Therapeutic Strategies

“…NSCs can differentiate into various types of neural cells, including neurons and glial cells [209]. In HD, specific types of neurons (such as MSNs in the striatum) undergo degeneration.…”

Potential roles of telomeres and telomerase in neurodegenerative diseases

“…ALS is a rapidly progressive and fatal NDD primarily affecting motor neurons in the motor cortex, brainstem, and spinal cord, with predominantly sporadic cases and inheritance in about 10% of cases [72] . Characterized by motor neuron death and dysfunction, it often presents with gliosis at lesion sites, thinning of spinal nerve anterior roots, axonal breaks, and demyelination [14] . The prevalence of ALS increases with age, being highest between the ages of 60 and 79, and there are gender differences, showing a male to female ratio of 1.35 [73] .…”

“…These conditions are marked by a progressive loss of neurons and are characterized by symptoms such as cognitive decline, cerebral atrophy, white matter degeneration, and the buildup of neuropathic proteins. Key examples include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and others [14] . The brain has limited nerve repair capacity, but this is insufficient to stop the disease from progressing [15] .…”