Cellular Transplantation as the Treatment of Alzheimer’s Disease in Mouse Models

Acetylcholine (Ach) and N-methyl-D-aspartate (NMDA) have been two major therapeutic targets of Alzheimer’s disease (AD) for decade. However, truly effective remedy for AD has not been successfully developed. We previously transplanted neurons derived from human induced pluripotent stem (hiPS) cells into the hippocampus of human amyloid precursor protein transgenic AD model mice. The cell transplantation significantly improved cognitive dysfunction in the dementia model mice. Human choline acetyl transferase (ChAT) positive cholinergic neurons located throughout the cortex of the grafted mice. Human and mouse ChAT positive neurons and alpha7 nicotinic acetylcholine receptor (α7nAChR) positive neurons significantly increased in the cortex and hippocampus of the grafted dementia mice compared with the vehicle injected dementia mice. Human and mouse vesicular GABA transporter (VGAT) positive neurons distributed mainly in the hippocampus and, though the number was small, human VGAT positive neurons located in the cortex. In the grafted mouse cortex, the number of GABA receptor (GABAR) positive neurons of both hiPS origin and mouse origin increased significantly compared with those in the vehicle injected mouse cortex. We suggested that positive feedback loops of neurotransmitter secretion of the cortex and hippocampus induced the characteristic distribution of the transplanted neurons. In this review, we summarized current advances in stem cell therapy for dementia model mice, especially to highlight the relationships between major neurotransmitters and host/transplanted neurons. *Corresponding author: Noboru Suzuki, Department of Immunology and Medicine and Department of Regenerative Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan, Tel: +81-44-977-8111; E-mail: [email protected] Received March 01, 2016; Accepted March 07, 2016; Published March 14, 2016 Citation: Suzuki N, Shimizu J, Fujiwara N, Arimitsu N (2016) Cellular Transplantation as the Treatment of Alzheimer’s Disease in Mouse Models. J Alzheimers Dis Parkinsonism 6: 219. doi: 10.4172/2161-0460.1000219 Copyright: © 2016 Suzuki N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This review focused on the usefulness of stem cell transplantation for the treatment of dementia models and we summarized their effects on the disease pathology and cognitive function in AD models. Neural Induction from Pluripotent Stem Cells In the first step of vertebrate development, cells which are committed to differentiate into neural cells are suggested to differentiate into anterior/rostral fate (forebrain cells) of central nervous system (CNS), mainly by bone morphogenetic protein (BMP) inhibitors [7]. After the cell fate acquisition, an appropriate regional patterning of CNS is provided by several organizing centers of the neural tube [8]. BMP and sonic hedgehog (SHH) are important molecules for the dorsalization and ventralization of neurons within the neural tube, respectively. Retinoic acid (RA) is a key molecule for the caudalization of the neurons towards midbrain, hindbrain and spinal cord neuron fate [7]. Because of the inherent limitation of experimental studies, underlying molecular mechanisms of human brain development remain largely unexplored. Citation: Suzuki N, Shimizu J, Fujiwara N, Arimitsu N (2016) Cellular Transplantation as the Treatment of Alzheimer’s Disease in Mouse Models. J Alzheimers Dis Parkinsonism 6: 219. doi: 10.4172/2161-0460.1000219