The Current Applications and Potential of Stem Cell-Derived Organoids

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 3394

Special Issue Editors


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Guest Editor
Institute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, Germany
Interests: iPSC-based disease modelling; Alzheimer's disease; Nijmegen breakage syndrome; steatosis patients; acute and chronic kidney injury
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E-Mail Website
Guest Editor
Institute of Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Dusseldorf, Germany
Interests: pluripotent stem cells; in vitro differentiation; hepatocytes; non alcoholic fatty liver disease; epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In addition to therapy, in vitro differentiated cells are currently used for drug testing, development, and disease modeling to give valuable insights into underlying mechanisms. Pluripotent stem cell (PSC)-derived 3D organoids are composed of distinct cell types characteristic within the organ under investigation and adopt specific organ-related structure, thus further increasing their maturity and utility compared to 2D cultured cells. Furthermore, the culturing of organoids employing organ-on-a-chip systems has added an additional level of sophistication and enhancement, thus enabling investigations at near-physiological levels.

Methodologies to attempt to create human 3D models from PSCs have been pursued since the late 2000s, with a breakthrough being achieved more recently with the generation of brain organoids. Tissue-specific organoids derived from PSCs are self-organizing structures which recapitulate with considerable accuracy the temporal developmental trajectory similar to fetal development. Notably, not only does the cyto-architecture of the organoids mimic aspects of the tissue-specific organ, but it also shares similar epigenetic and transcriptional programs. The exciting advances in the PSC-derived organoid field have opened up new avenues and tools for obtaining a better understanding of human development. However, organoid technology is still in an early phase of development, facing several challenges that limit their utility, and further optimization of the existing models is required. New robust and standardized protocols of differentiation and maturation of organoids, with increased cellular complexity while maintaining reproducibility, are needed. A combination of refined organoids systems with technological advances in the “-omics” methodologies and genome editing tools will increase our knowledge of healthy human development.

In this Special Issue, we invite researchers to contribute original research articles, comprehensive reviews, and communications on all aspects related to the utility of tissue-specific organoids as experimental systems for studying a normal healthy development and molecular mechanisms underlying diseases, toxicology and drug screening.

You may choose our Joint Special Issue in Organoids.

Prof. Dr. James Adjaye
Dr. Nina Graffmann
Guest Editors

Manuscript Submission Information

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Keywords

  • organoids
  • stem cell-derived organoids
  • stem cells
  • pluripotent stem cells
  • iPSCs
  • organ-on-a-chip
  • disease modelling
  • cellular therapeutics
  • regenerative medicine

Published Papers (2 papers)

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Research

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19 pages, 9745 KiB  
Article
Free Bilirubin Induces Neuro-Inflammation in an Induced Pluripotent Stem Cell-Derived Cortical Organoid Model of Crigler-Najjar Syndrome
by Abida Islam Pranty, Wasco Wruck and James Adjaye
Cells 2023, 12(18), 2277; https://doi.org/10.3390/cells12182277 - 14 Sep 2023
Viewed by 2009
Abstract
Bilirubin-induced neurological damage (BIND), which might progress to kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus enabling albumin-unbound free bilirubin (BF) to cross the blood–brain barrier and accumulate within. A defect in the UGT1A1 enzyme-encoding gene, which is [...] Read more.
Bilirubin-induced neurological damage (BIND), which might progress to kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus enabling albumin-unbound free bilirubin (BF) to cross the blood–brain barrier and accumulate within. A defect in the UGT1A1 enzyme-encoding gene, which is directly responsible for bilirubin conjugation, can cause Crigler–Najjar syndrome (CNS) and Gilbert’s syndrome. We used human-induced pluripotent stem cell (hiPSC)-derived 3D brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of BF in the developing human brain. Healthy and patient-derived iPSCs were differentiated into day-20 brain organoids, and then stimulated with 200 nM BF. Analyses at 24 and 72 h post-treatment point to BF-induced neuro-inflammation in both cell lines. Transcriptome, associated KEGG, and Gene Ontology analyses unveiled the activation of distinct inflammatory pathways, such as cytokine–cytokine receptor interaction, MAPK signaling, and NFκB activation. Furthermore, the mRNA expression and secretome analysis confirmed an upregulation of pro-inflammatory cytokines such as IL-6 and IL-8 upon BF stimulation. This novel study has provided insights into how a human iPSC-derived 3D brain organoid model can serve as a prospective platform for studying the etiology of BIND kernicterus. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Stem Cell-Derived Organoids)
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Review

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36 pages, 1311 KiB  
Review
Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies
by Douglas Bottega Pazzin, Thales Thor Ramos Previato, João Ismael Budelon Gonçalves, Gabriele Zanirati, Fernando Antonio Costa Xavier, Jaderson Costa da Costa and Daniel Rodrigo Marinowic
Cells 2024, 13(9), 745; https://doi.org/10.3390/cells13090745 - 25 Apr 2024
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Abstract
This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant [...] Read more.
This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Stem Cell-Derived Organoids)
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