# Models of Human Pluripotent Stem Cells

Samuel Riley

► To cite this version:

Samuel Riley. Models of Human Pluripotent Stem Cells. Cellular & Molecular Medicine: Open access, 2021, Models of Human Pluripotent Stem Cells, 7 (6). [https://doi.org/10.3389/fimmu.2021.002165](https://doi.org/10.3389/fimmu.2021.002165)

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Submitted on 16 Mar 2023

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Distributed under a Creative Commons Attribution 4.0 International License
# Models of Human Pluripotent Stem Cells

Samuel Riley*

Editorial Office, Cellular & Molecular
Medicine, Germany

## Abstract

For both target identification and drug discovery, it is critical to develop relevant and robust models for neurological illnesses. Glial cells' noncell autonomous effects on neurons have been documented in a wide spectrum of neurodegenerative and neurodevelopmental disorders, suggesting that neuroglial interactions might be a new therapeutic target. Surprisingly, the recent breakthrough finding of human induced pluripotent stem cells (hiPSCs) has paved the way for "in a dish" research into neurological and neurodevelopmental problems. Stem cells are undifferentiated or partly differentiated cells in multicellular animals that may specialise into many types of cells and multiply endlessly to create additional stem cells. In a cell lineage, they are the earliest form of cell. They can be present in both embryonic and adult organisms, although their characteristics differ slightly. Progenitor cells, which cannot divide endlessly, and precursor or blast cells, which are normally dedicated to developing into one cell type, are commonly distinguished. We present a brief review of current work researching neuroglial interactions using hiPSCs in a pathogenic setting, as well as a brief synthesis of recent work investigating neuroglial interactions using hiPSCs.

**Keywords:** Stem cells; Neuroglial; Progression-free survival; Human induced pluripotent stem cells

**\*Corresponding author:**

Samuel Riley

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hlchristensen@gmail.com

Editorial Office, Cellular & Molecular
Medicine, Germany

**Citation:** Riley S (2021) Models of Human Pluripotent Stem Cells. Cell Mol Med. Vol. 7 No. 6: 28.

**Received:** November 11, 2021, **Accepted:** November 24, 2021, **Published:** November 30, 2021

## Introduction

Although glial cells, such as trocytes, microglial cells, and oligodendrocytes, have long been thought to serve mainly as support for neuron activities, there has been a surge of interest in these cells in the last two decades, since their functions overlap with those formerly attributed to neurons [1]. Glial cells have been implicated in the development of a number of central nervous system disorders (CNS). Adult stem cells can only be found in a few habitats throughout the body, such as the bone marrow or the gonads. They are multipotent or unipotent, meaning they can only develop into a few cell types or just one kind of cell, and they exist to replenish rapidly lost cell types. Hematopoietic stem cells, which replace blood and immune cells, basal cells, which maintain the skin epithelium, and mesenchymal stem cells, which maintain bone, cartilage, muscle, and fat cells, are examples of these cells in mammals. Adult stem cells make up a small percentage of the total cell population; they are enormously outnumbered by the progenitor cells and terminally differentiated cells into which they develop. They pioneered work in mice that led to the discovery of the blood-forming stem cell, the hematopoietic stem cell

(HSC). McCulloch and Till started a series of studies in which they injected bone marrow cells into irradiated animals. The quantity of bone marrow cells injected resulted in lumps in the spleens of the mice, which were directly proportional to the number of cells injected. Each lump (colony) was thought to be a clone derived from a single marrow cell (stem cell). Furthermore, microglia, which were formerly thought to be only brain immune cells, are now recognised as critical players in neuronal patterning and synaptic wiring. Microglia operate as immunological surveyors and clean cellular trash in the brain in their "resting state," secreting cytokines and expressing neurotransmitter receptors similar to those found in neurons. As a result, they play a role in synaptic pruning, which is the process of removing synapses during brain growth. Microglial cells undergo morphological changes and migrate towards the areas of inflammation when they are "activated."

## Controlling the cell cycle

Embryonic stem cells (ESCs) have the potential to divide endlessly while maintaining pluripotency, thanks to specific cell cycle
regulatory systems. ESCs exhibit distinct cell cycle properties compared to proliferating somatic cells, such as fast cell division induced by shorter G1 phase, absence of G0 phase, and changes in cell cycle checkpoints. Cdk5 (cyclin-dependent protein kinases) are key components of the cell-cycle regulation system, and their activity is reliant on their connection with regulatory subunits termed cyclins. The commencement of various cell-cycle events is caused by oscillations in the activity of various cyclin-Cdk complexes, which leaves the cells primarily in S phase at any given moment. The low doubling duration of ESCs, which ranges from 8 to 10 hours, contrasts with the doubling time of somatic cells, which is around 20 hours or more. These features alter when cells differentiate: the G1 and G2 phases prolong, resulting in longer cell division cycles. The length of G1 in human ESCs (hESCs) is drastically reduced. This has been ascribed to high mRNA levels of G1-related Cyclin D2 and Cdk4 genes, as well as low levels of cell cycle regulatory proteins such p21CipP1, p27Kip1, and p57Kip2, which impede cell cycle progression at G1. Cdk4 and Cdk6 activity regulators, including as members of the Ink family of inhibitors (p15, p16, p18, and p19), are also expressed at low levels or not at all. hESCs, like mESCs, have a high Cdk activity, with Cdk2 kinase activity being the greatest. hESCs, like mESCs, highlight the role of Cdk2 in G1 phase control by showing that when Cdk2 activity is blocked, the transition from G1 to S is delayed and G1 is arrested. Initial techniques for obtaining mesDA from iPSCs relied on inefficient neural induction approaches such as coculture with stromal cells [46] and the induction of ventral midbrain identity using SHH and FGF8 signals. The description of the creation of floor plate cells from iPSCs [68], a process later employed for differentiation of iPSC into mesDA neurons, was the genuine breakthrough in the development of mesDA neurons. Human mesDA neurons need the simultaneous oral and concentration-dependent activation and/or inhibition of transcription factors morphogens emanating from signalling

centres, in addition to the neuroectodermal induction stage mediated by inhibition of both SMAD major pathways.

## Discussion

Stem cells go through two forms of cell division to guarantee self-renewal (see Stem cell division and differentiation diagram). Symmetric division produces two identical daughter cells, each having stem cell characteristics. In contrast, asymmetric division creates just one stem cell and a progenitor cell with low self-renewal capacity. Lineage analysis is a critical step in the analysis of growing embryos. Because cell lineages demonstrate the link between cells at each cycle. This aids in the identification of stem cell efficacy, lifetime, and other parameters by studying stem cell lineages along the route. Mutant genes in stem cell clones may be studied using the cell lineage approach, which can aid in genetic pathways. These pathways have the ability to control how stem cells function.

## Conclusion

Drug discovery campaigns using neurons derived from human iPSCs have been successful in a variety of diseases, including Alzheimer's disease (AD) on A142-induced cellular toxicity, ALS with TDP43 aggregation [153] and neuron survival, bipolar disorder on Wnt/catenin signalling modulation, and familial dysautonomia on rescued expression of IKBKAP. Moreover, dozens of medicines have been tried on neurons from patients with Friedreich's ataxia on the reactivation of the silenced Fmr1 gene, PD on MEF2C activity, and Niemann-Pick disease type C on lysosomal cholesterol buildup. The primary objective of these screening trials was to find medicines that could reverse the disease-related phenotype. Drug toxicity has been studied between iPSC-derived neurons and astrocytes to identify possible CNS side effects.