Stem Cell Therapies in Alzheimer’s Disease: Applications for Disease Modeling

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease with complex pathological and biological characteristics. Extracellular β-amyloid deposits, such as senile plaques, and intracellular aggregation of hyperphosphorylated tau, such as neurofibrillary tangles, remain the main neuropathological criteria for the diagnosis of AD. There is currently no effective treatment for the disease, and many clinical trials have failed to prove any benefits of new therapeutics. More recently, there has been increasing interest in harnessing the potential of stem cell technologies for drug discovery, disease modeling, and cell therapies, which have been utilized to study an array of human conditions, including AD. The recently developed and optimized induced pluripotent stem cells (iPSCs) technology is a critical platform for screening anti-AD drugs and understanding mutations that modify AD. Neural stem cells (NSCs) transplantation has been investigated as a new therapeutic approach to treat neurodegenerative diseases. Mesenchymal stem cells (MSCs) also exhibit considerable excitement to treat neurodegenerative diseases by secreting growth factors and exosomes, attenuating neuroinflammation. This review highlights recent progress in stem cell research and the translational applications and challenges of iPSCs, NSCs, and MSCs as treatment strategies for AD. Even though these treatments are still in relative infancy, these developing stem cell technologies hold considerable promise to combat AD and other neurodegenerative disorders.

Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease

“…Different type of stem cells such as embryonic SC can mitigate ACh levels [ 32 ], induced pluripotent SC can help in regeneration of depleted neural network [ 33 , 34 ] while umbilical cord blood/placenta and mesenchymal SC can reduce Aβ, tau phosphorylation and reverse microglial neuroinflammation [ 35 ]. Several clinical trials (phase1/2) involving autologous adipose tissue-derived mesenchymal stem cells (MSC), human MSC, leukemia MSC, bone marrow MSC and human umbilical cord blood-derived MSC have been conducted in the AD patients to evaluate their safety and efficacy [ 36 , 37 ]. Undoubtedly stem cell therapy has the potential to produce disease-modifying effects in AD and therefore cast a ray of hope in a battle against the devastating AD.…”

Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary Success

“…The long-term diseases of great importance to be considered are the Alzheimer's disease (AD) and the other neurodegenerative diseases for which therapy is a severe problem [72]. NSCs, the neural cells of the MSC type, are generated and distributed in the brain stromas.…”

“…Progress of translational applications based on these effects is still in a relative infancy. However, its stem technologies hold considerable promise to combat neurodegenerative diseases [72].…”

“…The form often employed to strengthen the early development of clinical practice is regenerative medicine, based on the EV-dependent regeneration of affected tissues such as the systems of brain, blood vessels and others [28,50,64,71,72,[107][108][109][110]. Critical for these processes, operative by cell-free strategy, is the successful translation of preclinical studies into clinical platforms [21,32,45].…”

Adipose tissue‐derived stem cells as a potential candidate in treatment of Alzheimer's disease: A systematic review on preclinical studies

“…Stem cells have the ability to differentiate into other cell types and the power of unlimited division and the possibility of using them in the process of cell therapy. 12 Stem cells can suppress neuroinflammation, which plays a key role in the pathogenesis of AD. 13 In this regard, as a potential candidate, stem cells have captured attention.…”