Potential application of human neural crest-derived nasal turbinate stem cells for the treatment of neuropathology and impaired cognition in models of Alzheimer’s disease

Abstract

Background Stem cell transplantation is a fascinating therapeutic approach for the treatment of many neurodegenerative disorders; however, clinical trials using stem cells have not been as effective as expected based on preclinical studies. The aim of this study is to validate the hypothesis that human neural crest-derived nasal turbinate stem cells (hNTSCs) are a clinically promising therapeutic source of adult stem cells for the treatment of Alzheimer’s disease (AD). Methods hNTSCs were evaluated in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) according to the effect of transplantation on AD pathology, including PET/CT neuroimaging, immune status indicated by microglial numbers and autophagic capacity, neuronal survival, and cognition, in a 5 × FAD transgenic mouse model of AD. Results We demonstrated that hNTSCs showed a high proliferative capacity and great neurogenic properties in vitro. Compared with hBM-MSC transplantation, hNTSC transplantation markedly reduced Aβ42 levels and plaque formation in the brains of the 5 × FAD transgenic AD mice on neuroimaging, concomitant with increased survival of hippocampal and cortex neurons. Moreover, hNTSCs strongly modulated immune status by reducing the number of microglia and the expression of the inflammatory cytokine IL-6 and upregulating autophagic capacity at 7 weeks after transplantation in AD models. Notably, compared with transplantation of hBM-MSCs, transplantation of hNTSCs significantly enhanced performance on the Morris water maze, with an increased level of TIMP2, which is necessary for spatial memory in young mice and neurons; this difference could be explained by the high engraftment of hNTSCs after transplantation. Conclusion The reliable evidence provided by these findings reveals a promising therapeutic effect of hNTSCs and indicates a step forward the clinical application of hNTSCs in patients with AD.

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology

“…For example, mesenchymal-like stem cells residing in the olfactory mucosa demonstrated the promyelination effect on oligodendrocyte precursor cell, while similar mesenchymal cells derived from bone marrow do not enhance myelination (28). Distinctions between MSC from different tissues define their specific use in regenerative medicine (29,30). Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy has developed a set of minimum criteria for defining multipotent mesenchymal stromal cells: (a) on the expression of certain proteins/genes, (b) the ability to adhere to plastic and (c) differentiate in vitro into osteoblasts, adipocytes, chondroblasts (31).…”

“…For example, mesenchymal-like stem cells residing in the olfactory mucosa demonstrated the promyelination effect on oligodendrocyte precursor cell, while similar mesenchymal cells derived from bone marrow do not enhance myelination (28). Distinctions between MSC from different tissues define their specific use in regenerative medicine (29,30).…”

Effect of co-treatment with mesenchymal stem cells and polyvinyl alcohol- coated selenium nanoparticles on rats with streptozotocin-induced Alzheimer's disease

“…The effectiveness of MSCs on memory has been reported in animal models of AD. Transplantation of human bone marrow-derived MSCs enhanced memory in FAD transgenic mice by reducing Aβ42 levels and increasing the survival of hippocampal neurons (Lim et al, 2021). In another study, administration of MSCs derived extracellular vesicles in the Aβ-injected rats caused an improvement in spatial memory via reduced levels of soluble Aβ1-4 and increased hippocampal neurons viability (Sha et al, 2021).…”

Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases

“…In recent years, promising targets closely related to the regulation of microglia autophagy have been explored by several teams through wet-lab experiments and clinical trials ( Table 2 ; Yan et al, 2017 ; Li Y. et al, 2019 ; Yin et al, 2019 ; Lim et al, 2021 ; Chung et al, 2022 ). Evidence shows miRNAs are important regulators of autophagy ( Xu et al, 2012 ).…”