Iron Oxide Nanoparticle-Incorporated Mesenchymal Stem Cells for Alzheimer’s Disease Treatment

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease with multifactorial pathogenesis. However, most current therapeutic approaches for AD target a single pathophysiological mechanism, generally resulting in unsatisfactory therapeutic outcomes. Recently, mesenchymal stem cell (MSC) therapy, which targets multiple pathological mechanisms of AD, has been explored as a novel treatment. However, the low brain retention efficiency of administered MSCs limits their therapeutic efficacy. In addition, autologous MSCs from AD patients may have poor therapeutic abilities. Here, we overcome these limitations by developing iron oxide nanoparticle (IONP)-incorporated human Wharton's jelly-derived MSCs (MSC-IONPs). IONPs promote therapeutic molecule expression in MSCs. Following intracerebroventricular injection, MSC-IONPs showed a higher brain retention efficiency under magnetic guidance. This potentiates the therapeutic efficacy of MSCs in murine models of AD. Furthermore, human Wharton's jellyderived allogeneic MSCs may exhibit higher therapeutic abilities than those of autologous MSCs in aged AD patients. This strategy may pave the way for developing MSC therapies for AD.

Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging

“…Various MNPs have been considered for the carriers of chemotherapeutic drugs due to their advantages of enhanced bioavailability, minimal side effects, appropriate degradation, and targeted delivery [ [87] , [88] , [89] , [90] , [91] , [92] , [93] , [94] , [95] , [96] ]. Ferroptosis-induction cancer nanomedicines utilizing MNPs have been produced and tested, a summary of which is provided in Table 2 .…”

Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

“…Reproduced from Ref. [118] with permission. (B) Illustration of neural stem cell (NSC) differentiation pathways in AD mice induced by chiral nanoparticles (NPs) under 808 nm NIR laser irradiation.…”

“…In addition, IONP‐loaded MSCs acquire magnetic properties and can be enriched in the brain parenchyma under an external magnetic field, reducing adverse effects caused by off‐target activity (Figure 7A). [118] In addition, MSCs and other exogenous stem cells (mainly pluripotent stem cells and neuronal stem cells [197] ) can be transformed into highly differentiated somatic cells. Traditionally, the differentiation behavior of stem cells is regulated by environmental factors, such as cytokines, nutritional status, and mechanical stress [198] .…”

Recent progress in the effect of magnetic iron oxide nanoparticles on cells and extracellular vesicles

“…In a heart repair experiment, Lee et al [ 119 ] found that the NVs of MSCs derived from IONPs (IONP NVs) contain more heart repair therapeutic molecules (RNA and proteins) than normal MSC-derived NVs, which are mediated by the intracellular signal transduction modification triggered by the incorporation and ionization of iron oxide. With the slow ionization and assimilation of IONPs in vivo [ 120 ], the treatment of MSCs by IONP can improve the expression of anti-inflammatory and tissue repair cytokines by activating the JNK signal pathway [ 119 , 121 , 122 ]. At the same time, the level of therapeutic molecules in the prepared magnetic EVs increased.…”