Novel Balance Mechanism Participates in Stem Cell Therapy to Alleviate Neuropathology and Cognitive Impairment in Animal Models with Alzheimer’s Disease

Abstract

Stem cell therapy improves memory loss and cognitive deficits in animal models with Alzheimer’s disease. The underlying mechanism remains to be determined, but it may involve the interaction of stem cells with hippocampal cells. The transplantation of stem cells alters the pathological state and establishes a novel balance based on multiple signaling pathways. The new balance mechanism is regulated by various autocrine and paracrine cytokines, including signal molecules that target (a) cell growth and death. Stem cell treatment stimulates neurogenesis and inhibits apoptosis, which is regulated by the crosstalk between apoptosis and autophagy—(b) Aβ and tau pathology. Aberrant Aβ plaques and neurofibrillary tau tangles are mitigated subsequent to stem cell intervention—(c) inflammation. Neuroinflammation in the lesion is relieved, which may be related to the microglial M1/M2 polarization—(d) immunoregulation. The transplanted stem cells modulate immune cells and shape the pathophysiological roles of immune-related genes such as TREM2, CR1, and CD33—(e) synaptogenesis. The functional reconstruction of synaptic connections can be promoted by stem cell therapy through multi-level signaling, such as autophagy, microglial activity, and remyelination. The regulation of new balance mechanism provides perspective and challenge for the treatment of Alzheimer’s disease.

Adipose tissue‐derived mesenchymal stem cells ameliorate cognitive impairment in Alzheimer's disease rat model: Emerging role of SIRT1

“…It is noteworthy here that MSCs were previously reported to promote neurogenesis through upregulation of various neurotrophic factors 66,79,80 . NGF is one of these neurotrophins; it promotes neuronal proliferation and neuroprotection 81 . Its decline has been reported to be responsible for cholinergic dysfunction in AD 82 .…”

“…66,79,80 NGF is one of these neurotrophins; it promotes neuronal proliferation and neuroprotection. 81 Its decline has been reported to be responsible for cholinergic dysfunction in AD. 82 In the current study, we found significantly lower NGF expression levels, both in the hippocampus and frontal cortex brain areas.…”

Targeting autophagy in Alzheimer’s disease: Animal models and mechanisms

“…Transplanted bone marrow-derived mesenchymal stem cells (BMMSCs) stimulate neurogenesis and inhibit apoptosis, regulated by crosstalk between apoptosis and autophagy ( Qin et al, 2021a ). BMMSCs can activate autophagy by increasing the expression of BECN1/Beclin-1 and LC3-II-positive autophagosomes in the hippocampus of APP/PS1 mice, thereby ameliorating Aβ accumulation, hyperphosphorylated tau pathology, and cognitive deficits ( Qin et al, 2021b ).…”

Cell Therapy for Alzheimer’s Disease Using Biomedical Cellular Products Based on Stem Cells: A Review of the Scientific Literature

“…НСК, сверхэкспрессирующие холинацетилтрансферазу, могут обратить вспять пространственную память и дефицит обучения [33]. Основные механизмы связаны с паракринным высвобождением нейропротекторных факторов, ослаблением смешанной протеинопатии (амилоидной и тау), иммуномодуляцией, ингибированием нейровоспаления и усилением нейрогенеза и синаптогенеза [23,34]. Однако присутствуют и проблемы использования трансплантации НСК: они могут в том числе дифференцироваться в ненейрональную глию, возможен туморогенез, используются такие пути введения, как внутригиппокампальная или внутрижелудочковая стереотаксическая инъекция, что является нежелательным явлением, особенно при нескольких применениях.…”

“…На данном этапе лечение лишь симптоматическое и базируется на ингибиторах ацетилхолинэстеразы, таких как донепезил, галантамин, ривастигмин и такрин, антагонисте рецептора N-метил-d-аспартата (NMDA), таком как мемантин, и на Aβ-направленном моноклональном антителе, таком как адуканумаб [19][20][21].  РЕЗУЛЬТАТЫ С помощью стратегии поиска определено шесть связанных статей [23,34,58,62,87]. Четыре дополнительных исследования было выявлено из других источников (поисковая система Google) [11,29,37].…”