Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2023; 15(6): 530-547
Published online Jun 26, 2023. doi: 10.4252/wjsc.v15.i6.530
Neural lineage differentiation of human pluripotent stem cells: Advances in disease modeling
Yuan-Wei Yan, Eddie S Qian, Lauren E Woodard, Julie Bejoy
Yuan-Wei Yan, Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, United States
Eddie S Qian, Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Lauren E Woodard, Julie Bejoy, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Lauren E Woodard, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37232, United States
Lauren E Woodard, Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States
Author contributions: Yuan Y and Bejoy J wrote the manuscript; Qian ES and Woodard LE edited the manuscript; all authors have read and approved the final manuscript.
Supported by the CTSA Award from the National Center for Advancing Translational Sciences to the Vanderbilt Institute for Clinical and Translational Research, No. UL1 TR002243; A Pilot and Feasibility Award from the NIDDK to the Vanderbilt Diabetes Research and Training Center, No. DK020593; and a VA MERIT Award, No. BX004845.
Conflict-of-interest statement: Lauren E Woodard and Julie Bejoy have two patent applications submitted on “Accelerated protocol for deriving podocytes from hiPSCs” and “nephron progenitor exosomes” listed below; Inventors: Bejoy J and Woodard LE accelerated the protocol for the differentiation of podocytes from human pluripotent stem cells. Patent Application filed August 26, 2022. PCT/US2022/075447; Inventors: Bejoy J and Woodard LE Nephron progenitor exosomes, patent Application filed October 6, 2022. PCT/US2022/077692.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Julie Bejoy, PhD, Research Fellow, Department of Medicine, Vanderbilt University Medical Center, 1161, No. 21 Avenue, Nashville, TN 37232, United States. julie.bejoy@vumc.org
Received: February 16, 2023
Peer-review started: February 16, 2023
First decision: February 28, 2023
Revised: March 14, 2023
Accepted: April 27, 2023
Article in press: April 24, 2023
Published online: June 26, 2023
Abstract

Brain diseases affect 1 in 6 people worldwide. These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer’s disease. Recent advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models, tissue culture models, and epidemiologic patient data that are commonly used to study brain disease. One innovative method by which to model human neurological disease is via the directed differentiation of human pluripotent stem cells (hPSCs) to neural lineages including neurons, astrocytes, and oligodendrocytes. Three-dimensional models such as brain organoids have also been derived from hPSCs, offering more physiological relevance due to their incorporation of various cell types. As such, brain organoids can better model the pathophysiology of neural diseases observed in patients. In this review, we will emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models.

Keywords: Induced pluripotent stem cells, Astrocytes, Oligodendrocytes, Microglia, Brain organoids, Assembloids

Core Tip: This review discusses recent advances in the field of disease modeling using human-induced pluripotent stem cell-derived neural cell types as well as organoids. It also discusses challenges that exist with current approaches, in addition to considerations for possible improvements that will further advance the field of disease modeling.