Recent Advances: Decoding Alzheimer’s Disease With Stem Cells

Abstract

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that destroys cognitive functions. Recently, a number of high-profile clinical trials based on the amyloid cascade hypothesis have encountered disappointing results. The failure of these trials indicates the necessity for novel therapeutic strategies and disease models. In this review, we will describe how recent advances in stem cell technology have shed light on a novel treatment strategy and revolutionized the mechanistic investigation of AD pathogenesis. Current advances in promoting endogenous neurogenesis and transplanting exogenous stem cells from both bench research and clinical translation perspectives will be thoroughly summarized. In addition, reprogramming technology-based disease modeling, which has shown improved efficacy in recapitulating pathological features in human patients, will be discussed.

Stem cells as a promising therapeutic approach for Alzheimer’s disease: a review

“…However, several Aβ-targeting treatments failed to restore neurocognitive function (Coric et al 2012;Doody et al 2013;Kile et al 2017). Actually, the "one alteration, one disease, one drug" strategy is not applied for AD (Kimura, 2016); therefore, different targets in the brain should be considered (Fang et al 2018). Moreover, therapeutic interventions should be introduced at the early AD stages (Tong et al 2015).…”

“…Stem cellbased-approach is still under development but rapid achievements indicate its therapeutic potential for reversing AD-associated neurodegeneration, as well as, improving cellular and structural functions (Lee et al 2015;Kwak et al 2018). This therapeutic potential might be partly attributed to the neurosecretory (paracrine) effect, as several neurotrophic factors are implicated in neuromodulation of various cellular functions that ameliorate the pathological features and neurocognition in AD animal models (Fang et al 2018). Stem cells are capable of spontaneous self-renewal and subsequent differentiation into specialized cells, such as neurons and glial cells (Eriksson et al 1998;Paspala et al 2009).…”

“…The mechanistic action of NSCs is regulated by metabolic processes such as oxygen consumption and energy production (Almeida and Vieira 2017;Fatt et al 2015;Wang et al 2012a). Mitochondrial dysfunction is implicated in AD progression (Swerdlow et al 2014); therefore, more research is required to estimate the connection between the metabolic switch of NSCs and AD pathogenesis (Fang et al 2018).…”

“…MSCs have several modulatory features such as accessibility, ease of handling, availability, and a broad range of differentiating potential (Divya et al 2012). MSCs are characterized by the Blood-Brain Barrier (BBB)-crossing ability, active homing ability, and efficient migratory capacity toward damaged brain regions; moreover, MSCs could be clinically used in AD patients, because of their less-invasive systemic administration (intravenously), without inducing tumorigenicity or immunogenicity, besides lacking ethical concerns (Oh et al 2015, Fang et al 2018.…”

“…Exosomes are cell-derived membrane vesicles that regulate physiological or pathological pathways through acting as mediators of cell-to-cell communication and transferring genetic information to recipient cells (Record et al 2011). Furthermore, administration of exosomes could represent an alternative therapy for AD (Fang et al 2018;El Andaloussi et al 2013). Intravenous administration of MSC-derived exosomes enhances functional recovery in stroke-induced rats (Bang et al 2016); this might be attributed to "miR delivery to target cells," thereby regulating the expression of genetic information and promoting a therapeutic response (Juranek et al 2013).…”