Organoids and Models from Stem Cells

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

Deadline for manuscript submissions: 31 August 2025 | Viewed by 2109

Special Issue Editors


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Guest Editor
Unistem-Laboratory of Biomedical Embryology and Tissue Engineering Chair of Anatomy and Histology, Università degli Studi di Milano, Milan, Italy
Interests: insulin-secreting cells; stem cell differentiation; stem cell culture; stem cell biology; regenerative medicine; tissue engineering; stem cells; ovary cell; culture differentiation; tissue regeneration

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Guest Editor
Unistem-Laboratory of Biomedical Embryology and Tissue Engineering Chair of Anatomy and Histology, Università degli Studi di Milano, Milan, Italy
Interests: epigenetics and gene regulation; morphology and functional imaging of cells; stem cell biology; development, developmental genetics, pattern formation and embryology in animals; gene therapy; cell therapy; regenerative medicine

Special Issue Information

Dear Colleagues,

The role of the cellular microenvironment and tissue architecture was firstly described in the pioneering studies carried out over 20 years ago by Dr. Mina Bissel in murine mammary cells. Her experiments demonstrated that growing mammary cells in a solution of extracellular matrix induced cells to cluster into 3D structures and to regain their ability to produce milk in vitro, showing a direct correlation between tridimensional organization and function preservation. These observations are presently regarded as the beginning of the 3D culture and organoid era. A lot has happened since then, and a great number of tridimensional cell culture platforms have been developed to create models that bridge the gap between the in vivo complexity and the oversimplified conventional two-dimension (2D) in vitro cultures. These newly created tridimensional cultures more accurately reflect what normally happens within the tissues of the living organisms, preserving the original cell–cell and cell–ECM interactions, ensuring cell proliferation, boosting differentiation, and maintaining cell morphology and behavior, alongside an optimal access to nutrients. These features greatly empower their predictive capability and may significantly reduce the need for experimental animal testing in drug screening, organ development, and disease mechanism studies.

In this Special Issue, we will collect reports, reviews, and protocols related to the generation of well-characterized, reproducible, highly predictive 3D in vitro platforms in which these concepts are being pursued to encourage and stimulate the scientific community to design and produce models for the laboratory that mimic cell guidance conditions as they occur in vivo, spanning from mechanical cues, such as stiffness and 3D architecture, to chemical and soluble factors that tune the cell microenvironment.

Prof. Dr. Tiziana A. L. Brevini
Prof. Dr. Georgia Pennarossa
Guest Editors

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Keywords

  • cellular microenvironment
  • 3D culture
  • organoid

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Published Papers (2 papers)

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Research

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21 pages, 10370 KiB  
Article
Modeling Early Stages of Trophectoderm–Endometrium Interactions Using Trophoblastic and Endometrial Organoids and the Generation of Lacunoids/Cystoids
by Islam M. Saadeldin, Budur Alshehri, Maha AlThubyani, Falah H. Almohanna, Goran Matic, Ayman A. Swelum, Serdar Coskun, Khalid A. Awartani and Abdullah M. Assiri
Cells 2025, 14(14), 1051; https://doi.org/10.3390/cells14141051 - 9 Jul 2025
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Abstract
This study presents the first successful generation and comprehensive characterization of trophoblastic organoids (TOs) and the derivation of three-dimensional cavity- or sac-like structures—termed lacunoids/cystoids—from sheep intracytoplasmic sperm injection (ICSI) embryos. TOs were generated from sheep ICSI embryos for the first time and were [...] Read more.
This study presents the first successful generation and comprehensive characterization of trophoblastic organoids (TOs) and the derivation of three-dimensional cavity- or sac-like structures—termed lacunoids/cystoids—from sheep intracytoplasmic sperm injection (ICSI) embryos. TOs were generated from sheep ICSI embryos for the first time and were shown to express trophoblastic markers at levels comparable to those in embryonic tissue. Detailed morphological characterization was conducted for both the TOs and the derived lacunoids/cystoids. Additionally, the TOs’ interactions with endometrial organoids (EOs), as well as those with preimplantation embryos, were investigated through co-culture experiments. The TOs expressed key trophoblastic markers, including CDX2, GATA3, syncytin-1, KRT18, KRT7, and Sox2, confirming their validity as a model for studying sheep trophoblast biology. The generation of lacunoids/cystoids from the TOs further revealed their structural and developmental characteristics, contributing valuable insights into early placental development and trophoblast-related pathologies. The TOs also supported extended embryonic development, and their co-culture with EOs induced dynamic changes in gene expression, particularly in angiogenesis-related genes, in both organoid types. This novel and reproducible in vitro model offers a reliable platform to study early placental development, effectively recapitulating the biological crosstalk between the trophectoderm and endometrium. The in-depth characterization of TOs and lacunoids/cystoids highlights their potential to advance our understanding of trophoblast differentiation and related developmental disorders. Full article
(This article belongs to the Special Issue Organoids and Models from Stem Cells)
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Review

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26 pages, 2167 KiB  
Review
Endometrial Organoids and Their Role in Modeling Human Infertility
by Abdullah Jabri, Mohamed Alsharif, Tasnim Abbad, Bader Taftafa, Abdulaziz Mhannayeh, Abdulrahman Elsalti, Fayrouz Attia, Tanveer Ahmad Mir, Islam Saadeldin and Ahmed Yaqinuddin
Cells 2025, 14(11), 829; https://doi.org/10.3390/cells14110829 - 3 Jun 2025
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Abstract
Endometrial organoids (EOs) have emerged as a powerful three-dimensional (3D) model for studying the human endometrium, offering new insights into infertility and reproductive disorders. These self-organizing miniature structures closely mimic the cellular composition, hormonal responsiveness, and functional characteristics of the endometrium, making them [...] Read more.
Endometrial organoids (EOs) have emerged as a powerful three-dimensional (3D) model for studying the human endometrium, offering new insights into infertility and reproductive disorders. These self-organizing miniature structures closely mimic the cellular composition, hormonal responsiveness, and functional characteristics of the endometrium, making them valuable preclinical tools for investigating implantation failure, endometrial receptivity, and disease pathophysiology. This review explores the role of EOs in reproductive medicine, with a focus on their applications in infertility research, environmental toxicology, and regenerative therapies. Traditional 2D cell cultures fail to capture the complexity of these physiological and pathological interactions, whereas organoids provide a physiologically relevant system for studying implantation mechanisms. Additionally, co-culture models incorporating stromal and immune cells have further enhanced our understanding of the maternal–fetal interface. Beyond modeling infertility, EOs hold significant promise for therapeutic applications. Advances in organoid transplantation have demonstrated potential for treating endometrial dysfunction-related infertility, including conditions such as Asherman’s syndrome and thin endometrium. Moreover, these models serve as a platform for drug screening and biomarker discovery, paving the way for personalized reproductive medicine. Despite their transformative potential, limitations remain, including the need for improved extracellular matrices, vascularization, and immune system integration. This review emphasizes the significant contributions of EOs to the field of infertility treatment and reproductive biology by examining recent advancements and emerging research. The continued refinement of these models would offer a paradigm for improving assisted reproductive technologies (ARTs) and regenerative medicine outcomes, offering new hope for individuals facing infertility challenges. Full article
(This article belongs to the Special Issue Organoids and Models from Stem Cells)
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