Advantages and challenges of using allogeneic vs. autologous sources for neuronal cell replacement in Parkinson’s disease: insights from non-human primate studies DOI Creative Commons
Marina E. Emborg, Jeanette M. Metzger,

Kevin A. D’Amour

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111297 - 111297

Published: March 1, 2025

Intracerebral grafting of dopamine-producing cells is proposed as a strategy to replace the typical neurons lost Parkinson's disease (PD) and improve PD motor symptoms. Non-human primate studies have provided clues on relationship between host's immune response success. Herein, we discuss how system differentially affects graft depending origin reflect advantages limitations paradigms utilized assess graft-related outcomes. We also consider new strategies minimize or circumvent immunological related preclinical research needed identify most promising approaches be translated into clinic.

Language: Английский

Human cerebral organoids — a new tool for clinical neurology research DOI Open Access
Oliver L. Eichmüller, Juergen A. Knoblich

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(11), P. 661 - 680

Published: Oct. 17, 2022

Language: Английский

Citations

176

Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids DOI Creative Commons
Bilal Çakir, Yoshiaki Tanaka, Ferdi Rıdvan Kiral

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 20, 2022

Microglia play a role in the emergence and preservation of healthy brain microenvironment. Dysfunction microglia has been associated with neurodevelopmental neurodegenerative disorders. Investigating function human health disease challenging due to limited models available. Here, we develop method generate functional cortical organoids (hCOs) from embryonic stem cells (hESCs). We apply this system study during inflammation induced by amyloid-β (Aβ). The overexpression myeloid-specific transcription factor PU.1 generates microglia-like hCOs, producing mhCOs (microglia-containing hCOs), that engraft mouse brain. Single-cell transcriptomics reveals acquire cell cluster an intact complement chemokine system. Functionally, protect parenchyma cellular molecular damage caused Aβ. Furthermore, mhCOs, observed reduced expression Aβ-induced genes apoptosis, ferroptosis, Alzheimer's (AD) stage III. Finally, assess AD-associated highly expressed response Aβ using pooled CRISPRi coupled single-cell RNA sequencing mhCOs. In summary, provide protocol can be used fundamental translational studies as model investigate

Language: Английский

Citations

104

iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer DOI

Dong Shin Park,

Tatsuya Kozaki, Satish Kumar Tiwari

et al.

Nature, Journal Year: 2023, Volume and Issue: 623(7986), P. 397 - 405

Published: Nov. 1, 2023

Language: Английский

Citations

104

Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer’s disease DOI Creative Commons
Mengmeng Jin, Ranjie Xu, Le Wang

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(7), P. 1135 - 1153.e8

Published: July 1, 2022

Language: Английский

Citations

100

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

98

Microglia-containing human brain organoids for the study of brain development and pathology DOI Creative Commons
Wendiao Zhang,

Jiamei Jiang,

Zhenhong Xu

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 96 - 107

Published: Dec. 6, 2022

Microglia are resident immune cells in the central nervous system, playing critical roles brain development and homeostasis. Increasing evidence has implicated microglia dysfunction pathogenesis of various disorders ranging from psychiatric to neurodegenerative diseases. Using a human cell-based model illuminate functional mechanisms will promote pathological studies drug development. The recently developed microglia-containing organoids (MC-HBOs), in-vitro three-dimensional cell cultures that recapitulate key features brain, have provided new avenue pathology. However, MC-HBOs generated different methods differ origin, proportion, fidelity within organoids, may produced inconsistent results. To help researchers develop robust reproducible recapitulates in-vivo signatures study pathology, this review summarized current used generate opinions on use for disease modeling studies.

Language: Английский

Citations

87

Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids DOI
Jiaxiang Wu, Jingliang Zhang, Xiaoling Chen

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(8), P. 2424 - 2437

Published: March 18, 2024

Language: Английский

Citations

23

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases DOI Creative Commons
Wendy Balestri, Ruchi Sharma, Victor Allisson da Silva

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 23, 2024

Abstract Parkinson’s disease (PD) and Alzheimer’s (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, familial factors. These diseases have distinct pathologies symptoms that linked to specific cell populations in brain. Notably, immune system has been implicated both diseases, with a particular focus on dysfunction microglia, brain’s resident cells, contributing neuronal loss exacerbating symptoms. Researchers use models neuroimmune gain deeper understanding physiological biological aspects these how they progress. Several vitro vivo models, including 2D cultures animal utilized. Recently, advancements made optimizing existing developing 3D organ-on-a-chip systems, holding tremendous promise accurately mimicking intricate intracellular environment. As result, represent crucial breakthrough transformation current treatments for PD AD offering potential conducting long-term disease-based modeling therapeutic testing, reducing reliance significantly improving viability compared conventional models. The application research marks prosperous step forward, providing more realistic representation complex interactions within system. Ultimately, refined aim aid quest combat mitigate impact debilitating patients their families.

Language: Английский

Citations

18

Microglia-like Cells Promote Neuronal Functions in Cerebral Organoids DOI Creative Commons
Ilkka Fagerlund, Antonios Dougalis, Anastasia Shakirzyanova

et al.

Cells, Journal Year: 2021, Volume and Issue: 11(1), P. 124 - 124

Published: Dec. 30, 2021

Human cerebral organoids, derived from induced pluripotent stem cells, offer a unique in vitro research window to the development of cortex. However, key player developing brain, microglia, do not natively emerge organoids. Here we show that erythromyeloid progenitors (EMPs), differentiated migrate and mature into microglia-like cells interact with synaptic material. Patch-clamp electrophysiological recordings population supported emergence more diversified neuronal phenotypes displaying repetitive firing action potentials, low-threshold spikes activity, while multielectrode array revealed spontaneous bursting activity increased power gamma-band oscillations upon pharmacological challenge NMDA. To conclude, within organoids promote network maturation recapitulate some aspects microglia-neuron co-development vivo, indicating could be useful biorealistic human platform for studying interactions.

Language: Английский

Citations

82

Human assembloids DOI Open Access
Sabina Kanton, Sergiu P. Paşca

Development, Journal Year: 2022, Volume and Issue: 149(20)

Published: Oct. 15, 2022

ABSTRACT Deconstructing and then reconstructing developmental processes ex vivo is crucial to understanding how organs assemble physiology can be disrupted in disease. Human 3D stem cell-derived systems, such as organoids, have facilitated this pursuit; however, they often do not capture inter-tissue or inter-lineage cellular interactions that give rise emergent tissue properties during development. Assembloids are self-organizing systems result from the integration of multiple organoids combination with missing cell types primary explants. Here, we outline concept assembloids present their applications for studying nervous system other tissues. We describe tools used probe manipulate delineate current challenges potential new approach interrogate development

Language: Английский

Citations

61