Advanced Modeling of Peripheral Neuro-Effector Communication and -Plasticity

Physiology ◽  
2020 ◽  
Vol 35 (5) ◽  
pp. 348-357 ◽  
Author(s):  
Pien A. Goldsteen ◽  
Amalia M. Dolga ◽  
Reinoud Gosens

The peripheral nervous system (PNS) plays crucial roles in physiology and disease. Neuro-effector communication and neuroplasticity of the PNS are poorly studied, since suitable models are lacking. The emergence of human pluripotent stem cells (hPSCs) has great promise to resolve this deficit. hPSC-derived PNS neurons, integrated into organ-on-a-chip systems or organoid cultures, allow co-cultures with cells of the local microenvironment to study neuro-effector interactions and to probe mechanisms underlying neuroplasticity.

Stem Cells ◽  
2015 ◽  
Vol 33 (6) ◽  
pp. 1759-1770 ◽  
Author(s):  
Mark Denham ◽  
Kouichi Hasegawa ◽  
Trevelyan Menheniott ◽  
Ben Rollo ◽  
Dongcheng Zhang ◽  
...  

2019 ◽  
Author(s):  
Koray D. Kaya ◽  
Holly Y. Chen ◽  
Matthew J. Brooks ◽  
Ryan A. Kelley ◽  
Hiroko Shimada ◽  
...  

ABSTRACTRetinal organoids generated from human pluripotent stem cells exhibit considerable variability in temporal dynamics of differentiation. To assess the maturity of neural retina in vitro, we performed transcriptome analyses of developing organoids from human embryonic and induced pluripotent stem cell lines. We show that the developmental variability in organoids was reflected in gene expression profiles and could be evaluated by molecular staging with the human fetal and adult retinal transcriptome data. We also demonstrated that addition of 9-cis retinal, instead of widely-used all-trans retinoic acid, accelerated rod photoreceptor differentiation in organoid cultures, with higher rhodopsin expression and more mature mitochondrial morphology evident by day 120. Our studies thus provide an objective transcriptome-based modality for determining the differentiation state of retinal organoids, which should facilitate disease modeling and evaluation of therapies in vitro.Summary StatementThree-dimensional organoids derived from human pluripotent stem cells have been extensively applied for investigating organogenesis, modeling diseases and development of therapies. However, substantial variations within organoids pose challenges for comparison among different cultures and studies. We generated transcriptomes of multiple distinct retinal organoids and compared these to human fetal and adult retina gene profiles for molecular staging of differentiation state of the cultures. Our analysis revealed the advantage of using 9-cis retinal, instead of the widely-used all-trans retinoic acid, in facilitating rod photoreceptor differentiation. Thus, a transcriptome-based comparison can provide an objective method to uncover the maturity of organoid cultures across different lines and in various study platforms.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Qian Zhu ◽  
Qiqi Lu ◽  
Rong Gao ◽  
Tong Cao

Neural crest stem cells (NCSCs) represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration.


2021 ◽  
Vol 22 (14) ◽  
pp. 7524
Author(s):  
Juliette Duchesne de Lamotte ◽  
Anselme Perrier ◽  
Cécile Martinat ◽  
Camille Nicoleau

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and are responsible for botulism, a fatal disorder of the nervous system mostly induced by food poisoning. Despite being one of the most potent families of poisonous substances, BoNTs are used for both aesthetic and therapeutic indications from cosmetic reduction of wrinkles to treatment of movement disorders. The increasing understanding of the biology of BoNTs and the availability of distinct toxin serotypes and subtypes offer the prospect of expanding the range of indications for these toxins. Engineering of BoNTs is considered to provide a new avenue for improving safety and clinical benefit from these neurotoxins. Robust, high-throughput, and cost-effective assays for BoNTs activity, yet highly relevant to the human physiology, have become indispensable for a successful translation of engineered BoNTs to the clinic. This review presents an emerging family of cell-based assays that take advantage of newly developed human pluripotent stem cells and neuronal function analyses technologies.


2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Salvatore Simmini ◽  
Allen C. Eaves ◽  
Sharon A. Louis ◽  
Wing Chang

Efficient and reproducible generation of tissue-specific organoids from Human Pluripotent Stem Cells (hPSCs) represents one of the key tools for reducing the use of animals in research. STEMCELL Technologies is committed to optimizing workflows that efficiently support the generation and maintenance of multiple types of organoid cultures derived from hPSCs.


2021 ◽  
Vol 1 (6) ◽  
Author(s):  
Antigoni Gogolou ◽  
Thomas J.R. Frith ◽  
Anestis Tsakiridis

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Ulrich ◽  
S Weinreich ◽  
R Haller ◽  
S Menke ◽  
R Olmer ◽  
...  

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