Glutamatergic Neurons Differentiated from Embryonic Stem Cells: An Investigation of Differentiation and Associated Diseases

Abstract

Neurons that have been derived from various types of stem cells have recently undergone significant study due to their potential for use in various aspects of biomedicine. In particular, glutamatergic neurons differentiated from embryonic stem cells (ESCs) potentially have many applications in both basic research and regenerative medicine. This review summarized the literatures published thus far and focused on two areas related to these applications. Firstly, these neurons can be used to investigate neuronal signal transduction during differentiation and this means that the genes/proteins/markers involved in this process can be identified. In this way, the dynamic spatial and temporal changes associated with neuronal morphology can be investigated relatively easily. Such an in vitro system can also be used to study how neurons during neurogenesis integrate into normal tissue. At the same time, the integration, regulation and functions of extracellular matrix secretion, various molecular interactions, various ion channels, the neuronal microenvironment, etc., can be easily traced. Secondly, the disease-related aspects of ESC-derived glutamatergic neurons can also be studied and then applied therapeutically. In the future, greater efforts are needed to explore how ESC-differentiated glutamatergic neurons can be used as a neuronal model for the study of Alzheimer’s disease (AD) mechanistically, to identify possible therapeutic strategies for treating AD, including tissue replacement, and to screen for drugs that can be used to treat AD patients. With all of the modern technology that is available, translational medicine should begin to benefit patients soon.

A consolidated review on stem cell therapy for treatment and management of Alzheimer's disease

“…However, there has been progress in the differentiation of hESCs into progenitor cells of the medial ganglion protrusion, which is essential because the medial ganglion protrusion (MGE) is critical in the development of the embryonic brain because it is responsible for the initialization of basal forebrain neurons (including BFCNs and intermediate gamma‐aminobutyric acid neurons). In this study, the reintroduction of these MGE‐like progenitor cells into the hippocampus of mice was highly comparable to those of the previous study, which indicated that the cells were capable of producing MGE 14,21,22 …”

“…Because of their poor teratoma establishment, unpredictable immune response, and rejection, ESCs have limited clinical usefulness. Furthermore, before they can be used in clinical research approved by the Food and Drug Administration, it is necessary to overcome the ethical disputes due to the development of these technologies 22 . Experiments with experimental ESCs have been conducted in various mouse models with varying degrees of success.…”

“…Furthermore, before they can be used in clinical research approved by the Food and Drug Administration, it is necessary to overcome the ethical disputes due to the development of these technologies. 22 Experiments F I G U R E 1 Various stem cells are used to combat Alzheimer's disease-like Bone marrow-derived mesenchymal stem cells, Umbilical cord mesenchymal stem cells, Human embryonic stem cells, adipose tissue-derived mesenchymal stem cells, Induced pluripotent stem cells, Neural stem cells, neural progenitor cells, olfactory ensheathing cells, Medial ganglionic eminence-like progenitor cells which have the potential to remove amyloid depositions in AD brain. Cholinergic basal forebrain neurons (BFCNs), severely damaged in AD patients, have been generated from human embryonic stem cells (hESCs), frequently used in this process.…”

“…In this study, the reintroduction of these MGE-like progenitor cells into the hippocampus of mice was highly comparable to those of the previous study, which indicated that the cells were capable of producing MGE. 14,21,22…”

Promoting Alzheimer’s disease research and therapy with stem cell technology

“…Great progress has been made in iPSCs in neural differentiation in recent years, and there are now many protocols for inducing or reprogramming stem cells to differentiate into different types of cells and neurons involved in AD pathogenesis, such as neural progenitor cells [ 9 ], microglia [ 1 ], astrocytes [ 134 ], oligodendrocytes [ 138 ], endothelial pericytes [ 3 ], glutamatergic, aminobutyric acidergic neurons [ 23 , 41 ], and basal forebrain neurons [ 90 ], resulting in the possibility to create physiologically relevant in vitro models and more promising means of AD treatment. In the following sections, the value and potential of stem cells and their derived 2D, 3D, and humanized animal models in AD mechanism research, drug screening, and cell therapy are further explored.…”