The Current Applications and Potential of Stem Cell-Derived Organoids

A special issue of Organoids (ISSN 2674-1172).

Deadline for manuscript submissions: 31 May 2025 | Viewed by 5187

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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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 Cells.

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

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Published Papers (2 papers)

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Research

17 pages, 7889 KiB  
Article
Heparin-Binding Epidermal-like Growth Factor (HB-EGF) Reduces Cell Death in an Organoid Model of Retinal Damage
by Michelle N. H. Tang, Mariya Moosajee, Najam A. Sharif, G. Astrid Limb and Karen Eastlake
Organoids 2024, 3(3), 148-164; https://doi.org/10.3390/organoids3030010 - 5 Jul 2024
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Abstract
In zebrafish and various mammalian species, HB-EGF has been shown to promote Müller glia proliferation and activation of repair mechanisms that have not been fully investigated in human retina. In the current study, 70- to 90-day-old human retinal organoids were treated with 20 [...] Read more.
In zebrafish and various mammalian species, HB-EGF has been shown to promote Müller glia proliferation and activation of repair mechanisms that have not been fully investigated in human retina. In the current study, 70- to 90-day-old human retinal organoids were treated with 20 μM 4-hydroxytamoxifen (4-OHT), and CRX, REC, NRL, PAX6, VIM, GFAP, and VSX2 gene and protein expression were assessed at various times points after treatment. Organoids with or without 4-OHT-induced damage were then cultured with HB-EGF for 7 days. We showed that 20 μM 4-OHT caused a reduction in the number of recoverin-positive cells; an increase in the number of TUNEL-positive cells; and downregulation of the photoreceptor gene markers CRX, NRL, and REC. Culture of organoids with HB-EGF for 7 days after 4-OHT-induced damage caused a marked reduction in the number of TUNEL-positive cells and small increases in the number of Ki67-positive cells and PAX6 and NOTCH1 gene expression. The current results suggest that treatment of human ESC-derived retinal organoids with 4-OHT may be used as a model of retinal degeneration in vitro. Furthermore, HB-EGF treatment of human retinal organoids increases proliferating Müller cells, but only after 4-OHT induced damage, and may be an indication of Muller reactivity in response to photoreceptor damage. Further studies will aim to identify factors that may induce Müller cell-mediated regeneration of the human retina, aiding in the development of therapies for retinal degeneration. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Stem Cell-Derived Organoids)
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22 pages, 4970 KiB  
Article
Single-Cell Assessment of Human Stem Cell-Derived Mesolimbic Models and Their Responses to Substances of Abuse
by Thomas P. Rudibaugh, Ryan W. Tam, R. Chris Estridge, Samantha R. Stuppy and Albert J. Keung
Organoids 2024, 3(2), 126-147; https://doi.org/10.3390/organoids3020009 - 20 Jun 2024
Viewed by 894
Abstract
The mesolimbic pathway connects ventral tegmental area dopaminergic neurons and striatal medium spiny neurons, playing a critical role in reward and stress behaviors. Exposure to substances of abuse during development and adulthood has been linked to adverse outcomes and molecular changes. The rise [...] Read more.
The mesolimbic pathway connects ventral tegmental area dopaminergic neurons and striatal medium spiny neurons, playing a critical role in reward and stress behaviors. Exposure to substances of abuse during development and adulthood has been linked to adverse outcomes and molecular changes. The rise of human cell repositories and whole-genome sequences enables human functional genomics ‘in a dish’, offering insights into human-specific responses to substances of abuse. Continued development of new models is needed, and the characterization of in vitro models is also necessary to ensure appropriate experimental designs and the accurate interpretation of results. This study introduces new culture conditions for generating medium spiny neurons and dopaminergic neurons with an early common media, allowing for coculture and assembloid generation. It then provides a comprehensive characterization of these and prior models and their responses to substances of abuse. Single-cell analysis reveals cell-type-specific transcriptomic responses to dopamine, cocaine, and morphine, including compound and cell-type-specific transcriptomic signatures related to neuroinflammation and alterations in signaling pathways. These findings offer a resource for future genomics studies leveraging human stem cell-derived models. Full article
(This article belongs to the Special Issue The Current Applications and Potential of Stem Cell-Derived Organoids)
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