Therapeutic Potential of Human Stem Cell Implantation in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive debilitating neurodegenerative disease and the most common form of dementia in the older population. At present, there is no definitive effective treatment for AD. Therefore, researchers are now looking at stem cell therapy as a possible treatment for AD, but whether stem cells are safe and effective in humans is still not clear. In this narrative review, we discuss both preclinical studies and clinical trials on the therapeutic potential of human stem cells in AD. Preclinical studies have successfully differentiated stem cells into neurons in vitro, indicating the potential viability of stem cell therapy in neurodegenerative diseases. Preclinical studies have also shown that stem cell therapy is safe and effective in improving cognitive performance in animal models, as demonstrated in the Morris water maze test and novel object recognition test. Although few clinical trials have been completed and many trials are still in phase I and II, the initial results confirm the outcomes of the preclinical studies. However, limitations like rejection, tumorigenicity, and ethical issues are still barriers to the advancement of stem cell therapy. In conclusion, the use of stem cells in the treatment of AD shows promise in terms of effectiveness and safety.

Keywords: Alzheimer’s disease; Induced pluripotent stem cells; embryonic stem cells; mesenchymal stem cells; neural stem cells; neurodegenerative disease; neurogenesis; stem cell therapy; stem cell transplantation; stem cells.

Figure 1

Mechanism of stem cell amelioration of cognition. Stem cells enhance formation of Syp, PSD-95, and MAP2, which can stimulate synaptogenesis. miRNA-146a is also secreted by stem cells and later taken up by astrocytes, leading to synaptogenesis. Stem cells can increase cholinergic neuron production in three ways: 1. increased Trk-dependent Akt/Gsk3β signaling, 2. differentiation into cholinergic cells, and 3. increased secretion of Ki-67, GFAP, SOX2, nestin, and HuD; increased secretion of β-catenin and neurogenin (Ngn); and increased production of cholinergic cells. Brain glucose metabolism is also increased after stem cell implantation through increased N-acetylaspartate (NAA) and glutamate secretion and decreased choline and myo-inositol secretion. Amyloid-β 40 & 42 are known to cause AD. Stem cells can alter APP processing through Akt/GSK3β signaling-mediated BACE1 expression and decrease β-secretase activity to decrease amyloid β concentration and improve cognition. Pericytes also have a role in AD. Transplantation of stem cells can inhibit pericyte loss to: 1. promote phagocytosis of amyloid-β, 2. transport amyloid-β across the BBB, 3. supply oxygen and metabolites to endothelial cells, and 4. increase angiogenesis and neurogenesis, which improves cognitive function. Stem cells have a potent effect on tau phosphorylation in AD. They decrease tau phosphorylation, leading to increased microtubule stabilization and healthier neurons, thereby ameliorating cognition [141].