Stem cells and derived growth factors in Alzheimer’s disease: mechanistic insights and translational perspectives

Alzheimer's disease (AD) is a significant healthcare concern due to the complex interactions between amyloid-β accumulation, tau pathology, neuroinflammation, synaptic dysfunction, and progressive neuronal death. Stem-cell-based therapies have demonstrated potential to treat this complex condition through immunomodulation, trophic support, and neuroregeneration. Beyond direct cell replacement, stem-cell-derived growth factors have important therapeutic functions by providing strong neurotrophic and cytoprotective effects. These bioactive compounds improve neuronal survival, restore synaptic plasticity, and reduce inflammatory cascades that accelerate the course of AD. Important growth factors that support increased neural resilience, cholinergic preservation, synaptic strengthening, and mitochondrial stabilization include BDNF, NGF, and IGF-1. The current study synthesizes molecular knowledge and new clinical data to assess the translational potential of stem cells and their growth-factor secretome. According to preclinical research, neural stem cells (NSCs) increase synaptic density and maintain cholinergic integrity in APP/PS1 mice, while mesenchymal stem cells (MSCs) lower amyloid burden, inhibit microglial activation, and improve memory. The stem-cell secretome offers a significant therapeutic benefit. BDNF increases synaptic plasticity, NGF promotes cholinergic survival, and IGF-1 improves mitochondrial function and diminishes oxidative stress and tau-mediated toxicity. However, significant obstacles impede clinical advancement. Therapeutic stability is limited by the risks of tumorigenicity, poor long-term engraftment, immunological rejection, and irregular blood-brain barrier penetration. Major challenges persist, such as manufacturing inconsistency, scalability limitations, and difficulties attaining controlled growth-factor dosing. To advance stem-cell-based techniques for significant AD alterations, these hurdles must be overcome by biomaterial optimization, modified secretomes, and standardized production platforms.