Human Stem Cells in Disease Modelling and Treatment (2nd Edition)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 4032

Editors


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Guest Editor
Faculty of Sciences and Technology, University of Azores-Polo de Ponta Delgada, Rua da Mãe de Deus, 9500-321 São Miguel, Azores, Portugal
Interests: stem cell; iPSC; disease modelling; retinal diseases; advanced therapies; cell therapy; regenerative medicine
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Guest Editor
Department of Regeneration and Cell Therapy, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Avda. Américo Vespucio 24, 41092 Seville, Spain
Interests: stem cells; genome editing; cell therapy; ATMPs; retinal degeneration; AMD; Stargardt; retinitis pigmentosa
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last few decades, human stem cells have gained significant attention in biomedical research due to their unprecedented applications, both in terms of disease modelling and therapy. In addition, although rodents have been widely used as a model, they often fail to mirror the pathophysiology of human diseases due to species-specific differences.

This Special Issue of Biomedicines aims to highlight the most recent advances in the field of human stem cell modelling, translation, and clinical application. Topics of interest include, but are not limited to, the following:

  • Novel applications of human stem cells to study disease mechanisms;
  • The use of human stem cells in regenerative medicine;
  • Obstacles related to the cGMP compliance of human stem cells in regenerative medicine applications;
  • Other limitations in the clinical translation of human stem cells for regenerative medicine.

Dr. Sofia M. Calado
Dr. Álvaro Plaza Reyes
Guest Editors

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Keywords

  • induced pluripotent stem cells (iPSCs)
  • embryonic stem cells (ESCs)
  • disease models
  • cell therapies
  • cell therapy medicinal products (CTMPs)
  • regenerative medicine

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Published Papers (3 papers)

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Research

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21 pages, 4603 KB  
Article
Impact of Silver-Coated Dressing on Adipose-Derived Stem Cells and Fibroblasts in 2D and 3D Cultures
by Alina Chelmuș-Burlacu, Eric Tang, Snejana Smolenschi-Palanciuc, Vlad Pieptu and Dragoș Pieptu
Biomedicines 2026, 14(4), 776; https://doi.org/10.3390/biomedicines14040776 - 29 Mar 2026
Viewed by 554
Abstract
Background/Objectives: The effects of silver-coated dressing on wound healing, including cytotoxicity, are controversial due to the limited and incongruous results of in vitro versus in vivo research. Multiple factors intervene in wound healing processes and scarring, including pro/anti-inflammatory and pro/anti-fibrosis markers. Herein, to [...] Read more.
Background/Objectives: The effects of silver-coated dressing on wound healing, including cytotoxicity, are controversial due to the limited and incongruous results of in vitro versus in vivo research. Multiple factors intervene in wound healing processes and scarring, including pro/anti-inflammatory and pro/anti-fibrosis markers. Herein, to elucidate reported differences between in vitro and in vivo results, the effects of silver-coated dressing on 2D and 3D mono- and cocultures of fibroblasts and adipose-derived stem cells (ADSC) were investigated. Methods: Migration profiles in 2D and 3D assays, α-smooth muscle actin and proliferation marker Ki-67 expression, TGF-β1, TGF-β3, IL-6 and IL-10 levels and/or gene expression were assessed on four culture constructs. Results: In 2D systems at 24 h, silver-treated ADSC monocultures displayed better migration abilities compared to cocultures with high fibroblast ratio. In contrast, changes in the sprouting pattern between treated and untreated samples were non-significant in 3D constructs. TGFβ-1 levels decreased post-treatment, while TGFβ-3 increased, especially in 3D models. IL-6 gene expression was up-regulated following silver exposure in 3D models, mainly for stem cells in mono- and cocultures. Conclusions: Experiment data on 3D constructs suggest that silver-coated dressings do not significant impede wound healing, whereas cytotoxic effects were more pronounced in the 2D cultures. These inconsistencies, also noted in the literature, invite a methodological discussion of the 2D setup implications, recommending 3D constructs as a more appropriate evaluation standard where observable effects are closer to in vivo conditions and more relevant for transfer to clinical applications. Full article
(This article belongs to the Special Issue Human Stem Cells in Disease Modelling and Treatment (2nd Edition))
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16 pages, 3294 KB  
Article
Mesenchymal Stem Cells Modulate Granulosa Cell Function Under Inflammatory and Hypoxic Conditions
by Kalina Belemezova, Milena Kostadinova, Tsvetelina Oreshkova, Ivaylo Vangelov, Maria Yunakova, Tanya Timeva and Ivan Bochev
Biomedicines 2026, 14(1), 27; https://doi.org/10.3390/biomedicines14010027 - 22 Dec 2025
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Abstract
Background/Objectives: Increasing evidence points to hypoxia and inflammation as two major causes of compromised ovarian function. Increased oxidative stress under hypoxic conditions can damage cellular components, leading to the dysfunction and apoptosis of granulosa cells (GCs). The inflammatory response induced by hypoxia may [...] Read more.
Background/Objectives: Increasing evidence points to hypoxia and inflammation as two major causes of compromised ovarian function. Increased oxidative stress under hypoxic conditions can damage cellular components, leading to the dysfunction and apoptosis of granulosa cells (GCs). The inflammatory response induced by hypoxia may further impair the function of the ovaries and contribute to the development of premature ovarian insufficiency (POI). In animal models of premature ovarian failure, research has demonstrated that the transplantation of mesenchymal stem cells (MSCs) can enhance reproductive outcomes, increase the number of functioning ovarian follicles, and restore estradiol production. However, the specific mechanisms underlying the observed positive results are not well understood. Methods: The present study provides a comparative analysis of how MSCs influence human GC function under inflammatory and hypoxic conditions, using three different experimental approaches: direct co-culture, indirect co-culture with transwell cell culture inserts, and treatment with MSC-derived conditioned medium (MSCcm). Results: Inflammation significantly suppressed GC estradiol secretion and increased apoptosis. MSCs increased estradiol secretion in normal and hypoxic culture conditions when co-cultured directly with GCs. Our results also showed that, under inflammation, MSCs tended to decrease GC proliferation and that hypoxia alone did not have an effect on GC estradiol secretion or proliferation. Conclusions: The study emphasizes the dual nature of MSCs, which largely determines their effects on other cell types, and the need for the condition-specific optimization of MSC therapies for ovarian regeneration. Full article
(This article belongs to the Special Issue Human Stem Cells in Disease Modelling and Treatment (2nd Edition))
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Review

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43 pages, 1997 KB  
Review
The Synthetic Extracellular Matrix as a Maestro of the In Vitro Stem Cell Niche: Orchestrating Fate and Function
by Subhajit Giri and Pratyush Rajesh
Biomedicines 2026, 14(2), 485; https://doi.org/10.3390/biomedicines14020485 - 23 Feb 2026
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Abstract
Human-induced pluripotent stem cells (hiPSCs) have an innate ability to differentiate into the three germ layers: the ectoderm, endoderm, and mesoderm. By using targeted differentiation methods and carefully controlling growth factors, morphogens, and signaling modulators, hiPSCs can be guided to develop into specific [...] Read more.
Human-induced pluripotent stem cells (hiPSCs) have an innate ability to differentiate into the three germ layers: the ectoderm, endoderm, and mesoderm. By using targeted differentiation methods and carefully controlling growth factors, morphogens, and signaling modulators, hiPSCs can be guided to develop into specific lineage cell types. For clinical applications of hiPSCs and their derivatives, it is crucial to use xenogen-free, chemically defined culture media, reagents, recombinant growth factors, morphogens, and extracellular matrix (ECM) scaffolds. One major obstacle is the widespread use of Matrigel as an hiPSC culture matrix. Matrigel, derived from Engelbreth–Holm–Swarm (EHS) mouse sarcoma, is an extract of basement membrane material with a complex, poorly defined, and variable composition. It also exhibits batch-to-batch variability in mechanical and biochemical properties and is difficult to modify, which limits its rational use in the production of therapeutic cells and organoids. Synthetic ECM matrices and scaffolds offer a promising alternative because they can have a fully defined composition, highly tunable physical properties, surface modifications, and functionalization with recombinant signaling peptides and growth factors. This provides a suitable microenvironment for hiPSC culture and the directed differentiation towards lineage-specific cells and organoid development, and can be used in clinical-grade tissue transplantation and regenerative medicine. Full article
(This article belongs to the Special Issue Human Stem Cells in Disease Modelling and Treatment (2nd Edition))
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