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Cells
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Advances in Human Pluripotent Stem Cells
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Advances in Human Pluripotent Stem Cells

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

Deadline for manuscript submissions: 10 July 2026 | Viewed by 10037

Editors

Dr. Peggy Arthur

E-Mail Website
Guest Editor
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
Interests: human induced pluripotent stem cells; retinal organoids; assembled organoids; ocular diseases; extracellular vesicles
Dr. Sangeetha Kandoi

E-Mail Website
Guest Editor
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218, USA
Interests: retinal organoids; regenerative medicine; photoreceptor replacement therapy; iPSC; cone-dominant animal models; disease modeling; drug therapy
Dr. Nagavendra Kommineni

E-Mail Website
Guest Editor
Thermo Fisher Scientific, Cincinnati, OH 45237, USA
Interests: drug delivery; nanomedicine; cancer therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, have fundamentally altered our understanding of human development, disease modeling, and regenerative medicine. Their unique capacities for self-renewal and differentiation into different cell types offer numerous opportunities for exploring cellular processes, modeling complex diseases, and developing novel therapeutic strategies. In recent years, there has been significant progress in the generation, characterization, and manipulation of hPSCs, including improvements in reprogramming efficiency, genome editing capabilities, and lineage-specific differentiation protocols. This Special Issue of Cells brings together cutting-edge research and comprehensive reviews that highlight the latest developments in hPSC biology. Our focus is on novel methodologies, key mechanistic insights, and the identification of promising translational applications. By bringing together these cutting-edge contributions, we aim to foster interdisciplinary collaboration and accelerate progress within the field of stem cell research.

Dr. Peggy Arthur
Dr. Sangeetha Kandoi
Dr. Nagavendra Kommineni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human pluripotent stem cells
  • embryonic stem cells
  • induced pluripotent stem cells
 

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Published Papers (5 papers)

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Research

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20 pages, 9322 KB  
Article
Modeling Human Hypertrophic Scars with Induced Pluripotent Stem-Cell-Derived Scar Organoids Versus Skin Organoids
by Hyun Mi Kim, Eun Jung Oh, Suin Kwak, Se Ok Han and Ho Yun Chung
Cells 2026, 15(11), 969; https://doi.org/10.3390/cells15110969 - 24 May 2026
Viewed by 1011
Abstract
Hypertrophic scars are characterized by excessive collagen deposition, fibrotic remodeling, and functional impairment. However, the ability of current models is limited in recapitulating human pathology. This study presents a novel approach using induced pluripotent stem cell-derived scar organoids to model hypertrophic scar characteristics [...] Read more.
Hypertrophic scars are characterized by excessive collagen deposition, fibrotic remodeling, and functional impairment. However, the ability of current models is limited in recapitulating human pathology. This study presents a novel approach using induced pluripotent stem cell-derived scar organoids to model hypertrophic scar characteristics in vitro. Following established protocols, human pluripotent stem cells were differentiated into skin organoids and induced fibrotic transformation by treatment with TGF-β1 (10 ng/mL) and hypoxia (5% O2) from day 45 onward. Scar organoids exhibited significant contraction and increased collagen I deposition compared with skin organoids. Immunofluorescence analysis showed reduced LHX2 expression, indicating loss of hair follicle development, while collagen I expression was significantly elevated. Dark-field imaging revealed marked morphological divergence between skin and scar organoids. RNA sequencing revealed distinct transcriptomic profiles. Expression of hair follicle-associated gene families (KRT and KRTAP) was upregulated in scar organoids, whereas epidermal structure-related genes (KRT4, KRT7, CLDN7, and WNT7) were downregulated. These findings demonstrate that iPSC-derived scar organoids successfully recapitulate key features of human hypertrophic scars, including excessive collagen production, loss of skin appendage development, and contractile behavior. This platform offers potential for future applications in drug screening, precision medicine, and understanding the molecular mechanisms underlying scar formation. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
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21 pages, 7122 KB  
Article
Multiscale Comparative Analyses of OVB-Organoids and Cerebral Organoids
by Jingyi Yang, Xue Zhang, Shuang Li and Zhixian Gao
Cells 2026, 15(8), 703; https://doi.org/10.3390/cells15080703 - 16 Apr 2026
Viewed by 816
Abstract
Organoid technology is critical for studying human brain development, but existing single-organoid culture systems fail to simulate inter-organ interactions (e.g., optic vesicle–brain) in embryogenesis. This study aimed to establish a more comprehensive in vitro model for early neurodevelopment. We established standardized protocols for [...] Read more.
Organoid technology is critical for studying human brain development, but existing single-organoid culture systems fail to simulate inter-organ interactions (e.g., optic vesicle–brain) in embryogenesis. This study aimed to establish a more comprehensive in vitro model for early neurodevelopment. We established standardized protocols for cerebral organoids and optic vesicle-containing brain organoids (OVB-organoids), and performed multiscale analyses using immunofluorescence and transcriptomics to compare the two models. Key differences in cellular composition, structure, function and development were found; OVB-organoids better simulated early retinal development, visual-related structures/functions, with specific VSX2 expression and consistent transcriptomic profiles. OVB-organoids are an improved model for early neurodevelopment, providing a reliable basis for exploring eye-brain coordinated development mechanisms and having broad applications in developmental biology, disease research and personalized healthcare. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
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14 pages, 1661 KB  
Article
Karyotypic Profiling of Induced Pluripotent Stem Cells Derived from a Xeroderma Pigmentosum Group C Patient
by Almaqdad Alsalloum, Natalia Mingaleva, Ekaterina Gornostal, Zoia Antysheva, Peter Sparber, Mikhail Skoblov, Victoria Pozhitnova, Tatiana Belysheva, Aygun Levashova, Ekaterina Kuznetsova, Yulia Suvorova, Julia Krupinova, Viktor Bogdanov, Alexej Abyzov, Olga Mityaeva and Pavel Volchkov
Cells 2025, 14(24), 1985; https://doi.org/10.3390/cells14241985 - 14 Dec 2025
Viewed by 963
Abstract
Xeroderma Pigmentosum group C (XP-C) is an autosomal recessive disorder caused by mutations in the XPC gene, leading to defective nucleotide excision repair. This defect leads to genomic instability and a profound cancer predisposition. To model this disease, we generated induced pluripotent stem [...] Read more.
Xeroderma Pigmentosum group C (XP-C) is an autosomal recessive disorder caused by mutations in the XPC gene, leading to defective nucleotide excision repair. This defect leads to genomic instability and a profound cancer predisposition. To model this disease, we generated induced pluripotent stem cells (iPSCs) from an XP-C patient carrying a novel homozygous nonsense mutation in the XPC gene (c.1830C>A). The resulting iPSCs demonstrated typical pluripotent characteristics, including expression of key markers and trilineage differentiation capability. However, genomic assessment revealed progressive karyotypic instability during extended culture. While initial whole-genome sequencing detected no major chromosomal abnormalities, subsequent G-banding analysis identified acquired trisomy 12 in two lines (CL12 and CL27) and a derivative X chromosome in a third line (CL30). These abnormalities were absent in early-passage analyses, indicating that they were acquired and selected for during extended culture. The acquisition of a derivative X chromosome in CL30, alongside recurrent trisomy 12, represents a unique cytogenetic signature likely attributable to the underlying XPC defect. We hypothesize that the loss of GG-NER creates a permissive genomic environment, accelerating the accumulation of DNA damage and chromosomal missegregation under replicative stress. This temporal divergence in genomic integrity highlights how culture pressures drive chromosomal evolution in XP-C iPSCs independently of initial reprogramming. Our findings emphasize that XP-C iPSCs require continuous genomic surveillance and provide a model for investigating how DNA repair deficiencies interact with in vitro culture stress. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
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Review

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29 pages, 1896 KB  
Review
Human Cardiac Organoids: Advances and Prospects from Construction to Preclinical Drug Evaluation
by Meng Chen, Tianyi Zhang, Sheng Yang, Yiru Niu, Yiling Ge, Zaozao Chen, Juan Zhang, Yuepu Pu, Zhongze Gu and Geyu Liang
Cells 2026, 15(1), 7; https://doi.org/10.3390/cells15010007 - 19 Dec 2025
Cited by 4 | Viewed by 2001
Abstract
Drug-induced cardiotoxicity (DICT) severely hampers drug development and threatens patient safety. Together with the growing global burden of cardiovascular disease, there is an urgent need to establish more predictive preclinical models. Recently, human pluripotent stem cell-derived cardiac organoids (hCOs) have emerged as a [...] Read more.
Drug-induced cardiotoxicity (DICT) severely hampers drug development and threatens patient safety. Together with the growing global burden of cardiovascular disease, there is an urgent need to establish more predictive preclinical models. Recently, human pluripotent stem cell-derived cardiac organoids (hCOs) have emerged as a promising three-dimensional in vitro model, achieving significant progress in simulating the complex structure and function of the human heart. However, existing reviews predominantly focus on technical construction or specific applications, lacking an integrated discussion of pathological model construction and their use under evolving regulatory frameworks. This review distinguishes itself by proposing a novel, holistic framework that bridges “construction technology,” “pathological modeling,” and “application evaluation.” We systematically categorize and summarize three major strategies for building hCO-based pathological models: patient-specific, gene-edited, and microenvironment-modulated approaches. Furthermore, we highlight the unique advantages of hCOs in preclinical drug assessment and detail their cutting-edge applications in early DICT warning, metabolism-related safety evaluation, and personalized drug evaluation. Finally, we address current challenges, including maturation and standardization, and outline future directions involving integration with organ-on-a-chip technology and artificial intelligence. This review aims to provide a theoretical foundation and roadmap toward more reliable and human-relevant drug development paradigms. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
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39 pages, 1418 KB  
Review
Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review
by Sama Thiab, Juberiya M. Azeez, Alekya Anala, Moksha Nanda, Somieya Khan, Alexandra E. Butler and Manjula Nandakumar
Cells 2025, 14(15), 1188; https://doi.org/10.3390/cells14151188 - 1 Aug 2025
Cited by 5 | Viewed by 4596
Abstract
Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired [...] Read more.
Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
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