Application of Human Brain Organoids—Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases DOI Open Access
S.Y. Kim, Mi‐Yoon Chang

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12528 - 12528

Published: Aug. 7, 2023

Brain organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that reflect early brain organization. These contain different cell types, including neurons and glia, similar to those found in the brain. Human provide unique opportunities model features of development not well-reflected animal models. Compared with traditional cultures models, offer a more accurate representation function, rendering them suitable models for neurodevelopmental diseases. In particular, patients’ have enabled researchers study diseases at stages gain better understanding disease mechanisms. Multi-brain regional assembloids allow investigation interactions between distinct regions while achieving higher level consistency molecular functional characterization. Although possess promising features, their usefulness is limited by several unresolved constraints, cellular stress, hypoxia, necrosis, lack high-fidelity maturation, circuit formation. this review, we discuss studies overcome natural limitations organoids, emphasizing importance combinations all neural such as glia (astrocyte, oligodendrocytes, microglia) vascular cells. Additionally, considering similarity developing brain, regionally patterned organoid-derived (NSCs) could serve scalable source replacement therapy. We highlight potential application therapy within field.

Language: Английский

Human disease models in drug development DOI Open Access

Anna Loewa,

James J. Feng, Sarah Hedtrich

et al.

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(8), P. 545 - 559

Published: May 11, 2023

Language: Английский

Citations

139
An in vivo neuroimmune organoid model to study human microglia phenotypes DOI Open Access
Simon T. Schafer, Abed AlFatah Mansour, Johannes C. M. Schlachetzki

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(10), P. 2111 - 2126.e20

Published: May 1, 2023

Language: Английский

Citations

119
Advancing cell therapy for neurodegenerative diseases DOI Creative Commons
Sally Temple

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 512 - 529

Published: April 20, 2023

Language: Английский

Citations

91
Structural and functional integration of human forebrain organoids with the injured adult rat visual system DOI Creative Commons
Dennis Jgamadze,

James Lim,

Zhijian Zhang

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(2), P. 137 - 152.e7

Published: Feb. 1, 2023

Language: Английский

Citations

82
New and emerging approaches to treat psychiatric disorders DOI
Katherine W. Scangos, Matthew W. State, Andrew H. Miller

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(2), P. 317 - 333

Published: Feb. 1, 2023

Language: Английский

Citations

74
Genetics of human brain development DOI
Yi Zhou, Hongjun Song, Guo‐li Ming

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: Английский

Citations

69
A microscale soft ionic power source modulates neuronal network activity DOI Creative Commons
Yujia Zhang, Jorin Riexinger,

Xingyun Yang

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7976), P. 1001 - 1006

Published: Aug. 30, 2023

Abstract Bio-integrated devices need power sources to operate 1,2 . Despite widely used technologies that can provide large-scale targets, such as wired energy supplies from batteries or wireless transduction 3 , a efficiently stimulate cells and tissues on the microscale is still pressing. The ideal miniaturized source should be biocompatible, mechanically flexible able generate an ionic current for biological stimulation, instead of using electron flow in conventional electronic 4–6 One approach use soft inspired by electrical eel 7,8 ; however, combine required capabilities have not yet been produced, because it challenging obtain units both conserve contained before usage are easily triggered produce output. Here we develop depositing lipid-supported networks nanolitre hydrogel droplets internal ion gradients energy. Compared original eel-inspired design 7 our shrink volume unit more than 10 5 -fold store longer 24 h, enabling operation on-demand with 680-fold greater density about 1,300 W m −3 Our droplet device serve biocompatible modulate neuronal network activity three-dimensional neural microtissues ex vivo mouse brain slices. Ultimately, ionotronic might integrated into living organisms.

Language: Английский

Citations

68
Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications DOI Creative Commons

Jonas Cerneckis,

Hongxia Cai,

Yanhong Shi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 26, 2024

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable genetic engineering, can be differentiated into most somatic types. been widely applied model human development diseases, perform drug screening, develop therapies. In this review, we outline key developments iPSC field highlight immense versatility of modeling therapeutic applications. We begin by discussing pivotal discoveries that revealed potential a nucleus reprogramming led successful generation iPSCs. consider molecular mechanisms dynamics as well numerous methods available induce pluripotency. Subsequently, discuss various iPSC-based cellular models, from mono-cultures single type complex three-dimensional organoids, how these models elucidate diseases. use examples neurological disorders, coronavirus disease 2019 (COVID-19), cancer diversity disease-specific phenotypes modeled using iPSC-derived cells. also used high-throughput screening toxicity studies. Finally, process developing autologous allogeneic therapies their alleviate

Language: Английский

Citations

68
Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models DOI Open Access
Ornella Urzì, Roberta Gasparro, Elisa Costanzo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12046 - 12046

Published: July 27, 2023

Although historically, the traditional bidimensional in vitro cell system has been widely used research, providing much fundamental information regarding cellular functions and signaling pathways as well nuclear activities, simplicity of this does not fully reflect heterogeneity complexity vivo systems. From arises need to use animals for experimental research testing. Nevertheless, animal experimentation presents various aspects complexity, such ethical issues, which led Russell Burch 1959 formulate 3R (Replacement, Reduction, Refinement) principle, underlying urgent introduce non-animal-based methods research. Considering this, three-dimensional (3D) models emerged scientific community a bridge between models, allowing achievement differentiation while avoiding The purpose review is provide general overview most common establish 3D culture discuss their promising applications. Three-dimensional cultures have employed study both organ physiology diseases; moreover, they represent valuable tool studying many cancer. Finally, possibility using drug screening regenerative medicine paves way development new therapeutic opportunities diseases.

Language: Английский

Citations

50
Antisense oligonucleotide therapeutic approach for Timothy syndrome DOI Creative Commons
Xiaoyu Chen, Fikri Birey, Min-Yin Li

et al.

Nature, Journal Year: 2024, Volume and Issue: 628(8009), P. 818 - 825

Published: April 24, 2024

Abstract Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT and other neuropsychiatric conditions 1 . TS type (TS1) caused gain-of-function variant in the alternatively spliced developmentally enriched CACNA1C exon 8A, as opposed to its counterpart 8. We previously uncovered several phenotypes neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction an unanticipated persistent expression of 8A 2–6 reasoned that switching utilization 8 would represent potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) effectively decrease inclusion human cells both vitro and, following transplantation, vivo. discovered ASO-mediated switch robustly rescued defects patient-derived cortical organoids migration forebrain assembloids. Leveraging transplantation platform 7 , found single intrathecal ASO administration changes vivo patient neurons, suggesting suppression treatment for TS1. Broadly, these experiments illustrate how multilevel, stem cell model-based approach can identify strategies reverse disease-relevant neural pathophysiology.

Language: Английский

Citations

49