Stem cells in central nervous system diseases: promising therapeutic strategies

Diseases of the central nervous system (CNS) are a major cause of death and disability.

Given that CNS neurons are incapable of self-renewal during maturation, their loss is irreversible after injury or disease. It often leads to functional disorders.

Unfortunately, treatment options for CNS diseases are still limited and effective treatments for these notorious diseases need to be explored.

Stem cell therapy has emerged as a potential therapeutic strategy to improve the prognosis of CNS diseases.

Accumulating preclinical and clinical evidence has shown that multiple molecular mechanisms, such as cell replacement, immune regulation, and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases.

This review article aims to summarize the role and basic mechanisms of stem cell therapy in the treatment of CNS diseases. and is worth further evaluation for potential therapeutic applications of stem cell therapy in CNS disease.

Central Nervous System (CNS) Diseases

CNS diseases are among the most common disorders that affect the nervous system and lead to irreversible damage and loss of function.

These diseases are associated with high mortality and disability rates and impose a significant burden on society

Neurons in the CNS of mature mammals were believed to lack the ability to spontaneously regenerate following injury.

Therapeutic options for CNS diseases are often hindered by the complex and incompletely understood mechanisms of their pathogenesis.

CNS injuries such as stroke, spinal cord injury (SCI) and traumatic brain injury (TBI) trigger a cascade of deleterious events that severely affect neurological health.

Consequently, there is an urgent need for therapeutic strategies that can facilitate the restoration of neuronal function in the CNS.

Stem cell therapy

Stem cell therapy has attracted considerable attention as a prospective treatment method for CNS diseases.

The stem cells used include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs) and other types of stem cells.

Mesenchymal stem cells

Mesenchymal stem cells have the ability to self-renew and multi-directionally differentiate into cell types and can be derived from almost any type of tissue.

In addition, MSCs exert neuroprotective function through the secretion of neurotrophic growth factors and other mechanisms.

Stem cell therapy for neurological diseases

Stem cell therapy has emerged as a valuable approach in the treatment of various CNS diseases, especially neurodegenerative diseases.

Neurological diseases are characterized by progressive degeneration and loss of neurons in terms of structure, function or quantity.

PD, AD and ALS are the three main neurodegenerative diseases. Current drug treatments and surgical interventions for neurological diseases are not able to effectively stop the degenerative processes.

Today, stem cell therapy offers promising strategies to address a wide variety of neurological diseases.

Parkinson’s disease

Parkinson

PD is a common progressive neurodegenerative disorder characterized by dopamine (DA) deficiency in the striatum.

The current primary treatment approach for PD involves the administration of levodopa, a DA precursor, to compensate for DA deficiency caused by the destruction of dopaminergic neurons. While drug therapy can reduce symptoms, it does not stop or reverse the progression of neurodegeneration.

Transplantation of human embryonic dopaminergic neurons into the striatum of PD patients holds promise as a potential treatment (Freed et al., 2001). Transplanted stem cells have been shown to survive in patients with severe PD and successfully differentiate into functional DA neurons and resume DA production (Piccini et al., 1999). However, the clinical efficacy of stem cell transplantation is variable, possibly due to differences between transplanted cells (Olanow et al., 2003). Despite the challenges in generating the right type of DA neurons and improving conditions to increase the survival of transplanted cells, there is optimism about the potential of stem cells to induce the generation of functional DA neurons and serve as a form of cell therapy (Kim, 2011).

Alzheimer’s disease

Alzheimer

AD is the most common cause of dementia. The primary pathological mechanism of AD involves the accumulation of amyloid-β (Aβ) protein, which leads to the degeneration and loss of neurons and synapses in various brain regions.

The cholinergic system plays an important role in regulating learning and memory. Hence, the use of acetylcholinesterase inhibitors (AChEI) can partially reduce cognitive impairment in AD.

Because drug therapy for AD is primarily palliative and does not slow or reverse disease progression, effective treatment options are needed to meet the needs of AD patients.

Stem cell therapy for AD holds promise in meeting this need.

Transplantation of NSCs has shown promise in enhancing endogenous neurogenesis and preventing further cognitive decline, as evidenced by animal experiments.

However, the therapeutic potential of NSCs can be hindered by pathologically high levels of oxidative stress, which can damage neurons and impair neurogenic effects.

Current strategies primarily focus on directing the differentiation of NSCs into neurons and optimizing microenvironmental components to promote neurogenesis.

Integrating NSC transplantation with gene editing, nanomaterials, pharmacological interventions, and other approaches to improve the efficacy of stem cell therapy has been explored.

Nevertheless, the transition from animal experiments to clinical applications still requires considerable research efforts.

reference

Ying C, Zhang J, Zhang H, Gao S, Guo X, Lin J, Wu H, Hong Y. Stem cells in central nervous system diseases: Promising therapeutic strategies. Experimental Neurology. 2023 Sep 22:114543.

Article link

https://www.sciencedirect.com/science/article/pii/S0014488623002285