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Cells
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Advances and Breakthroughs in Stem Cell Research
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Advances and Breakthroughs in Stem Cell Research

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

Deadline for manuscript submissions: 20 March 2026 | Viewed by 10745

Special Issue Editors

Dr. Alexander E. Kalyuzhny

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Guest Editor
Dental Basic Sciences, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, USA
Interests: investigating the mechanisms underlying the constitutive induced heteromerization of opioid receptors
Special Issues, Collections and Topics in MDPI journals
Dr. Hemant Kumar Mishra

E-Mail
Guest Editor
Cellinfinitybio, San Francisco, CA, USA
Interests: induced pluripotent stem cell-derived NK and T cells; hematopoietic stem cells; cancer immunotherapy; therapeutic antibody; host-pathogen interaction; immune dysfunction; off the shelf therapy; checkpoint inhibitors; metalloproteases; small molecule inhibitors; cardiovascular disorders; tuberculosis; sarcoidosis; allergy and asthma

Special Issue Information

Dear Colleagues,

This Special Issue will center around the latest cutting-edge breakthroughs in stem cell research within immunotherapy and regenerative medicine. In recent years, advancements in stem cell research have opened promising avenues for treating and potentially curing diverse conditions such as cancers, metabolic disorders, and neurodegenerative diseases. The immense potential of specific human iPSC-derived cell lineages, including CAR T cells, CAR NK cells, neurons, cardiomyocytes, and pancreatic islets, holds transformative possibilities in revolutionizing medical practices through the development of innovative therapies. This Special Issue will explore a range of topics related to stem cell therapy, encompassing iPSC (induced pluripotent stem cell)- or hematopoietic-stem-cell-derived, therapeutically relevant lineages. We welcome original manuscripts and reviews that delve into these subjects, contributing to a more profound comprehension of recent advancements and challenges in these domains.

Prof. Dr. Alexander E. Kalyuzhny
Dr. Hemant Kumar Mishra
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 short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind 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

  • stem cell
  • induced pluripotent stem cell
  • iPSC
  • hematopoietic stem cell

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Published Papers (5 papers)

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Research

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17 pages, 4521 KB  
Article
A Novel Recombinant Vitronectin Variant Supports the Expansion and Differentiation of Pluripotent Stem Cells in Defined Animal-Free Workflows
by Xi Lu, Eli Perr, Tahmina Naqvi, David Galitz, Marnelle Andersen, David Grabowski, Anthony Person, Alex Kalyuzhny and Kevin C. Flynn
Cells 2024, 13(18), 1566; https://doi.org/10.3390/cells13181566 - 17 Sep 2024
Cited by 2 | Viewed by 2420
Abstract
An essential aspect of harnessing the potential of pluripotent stem cells (PSCs) and their derivatives for regenerative medicine is the development of animal-free and chemically defined conditions for ex vivo cultivation. PSCs, including embryonic and induced PSCs (iPSCs), are in the early stages [...] Read more.
An essential aspect of harnessing the potential of pluripotent stem cells (PSCs) and their derivatives for regenerative medicine is the development of animal-free and chemically defined conditions for ex vivo cultivation. PSCs, including embryonic and induced PSCs (iPSCs), are in the early stages of clinical trials for various indications, including degenerative diseases and traumatic injury. A key step in the workflows generating these cells for more widespread clinical use is their safe and robust ex vivo cultivation. This entails optimization of cell culture media and substrates that are safe and consistent while maintaining robust functionality. Here, we describe the design of a human vitronectin (hVTN) variant with improved manufacturability in a bacterial expression system along with improved function in comparison to wild-type VTN and other previously characterized polypeptide fragments. In conjunction with an animal component-free media formulation, our hVTN fragment provides animal-free conditions for the enhanced expansion of iPSCs. This hVTN variant also supports the reprogramming of PBMCs into iPSCs. Furthermore, we show that these iPSCs can be efficiently differentiated into the three major germ layers and cortical neurons, thereby closing the loop on a completely defined animal-free workflow for cell types relevant for regenerative medicine. Full article
(This article belongs to the Special Issue Advances and Breakthroughs in Stem Cell Research)
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17 pages, 26759 KB  
Article
A Novel CRISPR-Cas9 Strategy to Target DYSTROPHIN Mutations Downstream of Exon 44 in Patient-Specific DMD iPSCs
by Neha R. Dhoke, Hyunkee Kim, Karim Azzag, Sarah B. Crist, James Kiley and Rita C. R. Perlingeiro
Cells 2024, 13(11), 972; https://doi.org/10.3390/cells13110972 - 4 Jun 2024
Cited by 10 | Viewed by 4377
Abstract
Mutations in the DMD gene cause fatal Duchenne Muscular Dystrophy (DMD). An attractive therapeutic approach is autologous cell transplantation utilizing myogenic progenitors derived from induced pluripotent stem cells (iPSCs). Given that a significant number of DMD mutations occur between exons 45 and 55, [...] Read more.
Mutations in the DMD gene cause fatal Duchenne Muscular Dystrophy (DMD). An attractive therapeutic approach is autologous cell transplantation utilizing myogenic progenitors derived from induced pluripotent stem cells (iPSCs). Given that a significant number of DMD mutations occur between exons 45 and 55, we developed a gene knock-in approach to correct any mutations downstream of exon 44. We applied this approach to two DMD patient-specific iPSC lines carrying mutations in exons 45 and 51 and confirmed mini-DYSTROPHIN (mini-DYS) protein expression in corrected myotubes by western blot and immunofluorescence staining. Transplantation of gene-edited DMD iPSC-derived myogenic progenitors into NSG/mdx4Cv mice produced donor-derived myofibers, as shown by the dual expression of human DYSTROPHIN and LAMIN A/C. These findings further provide proof-of-concept for the use of programmable nucleases for the development of autologous iPSC-based therapy for muscular dystrophies. Full article
(This article belongs to the Special Issue Advances and Breakthroughs in Stem Cell Research)
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Review

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28 pages, 1478 KB  
Review
Safety Assessment of Stem Cell-Based Therapies: Current Standards and Advancing Frameworks
by Georgy E. Leonov, Lydia R. Grinchevskaya, Oleg V. Makhnach, Marina V. Samburova, Dmitry V. Goldshtein and Diana I. Salikhova
Cells 2025, 14(21), 1660; https://doi.org/10.3390/cells14211660 - 23 Oct 2025
Viewed by 817
Abstract
Regenerative medicine is a rapidly evolving field of contemporary biomedical research that offers new therapeutic strategies for conditions previously considered untreatable. Cell therapy shows particular potential in this domain. However, rigorous biosafety measures are required in its development and clinical application. This review [...] Read more.
Regenerative medicine is a rapidly evolving field of contemporary biomedical research that offers new therapeutic strategies for conditions previously considered untreatable. Cell therapy shows particular potential in this domain. However, rigorous biosafety measures are required in its development and clinical application. This review proposes a practice-oriented biosafety framework for cell therapy, translating key risks into operational principles: toxicity, oncogenicity/tumorigenicity/teratogenicity, immunogenicity, biodistribution; and cell product quality. For each principle, preclinical approaches and regulatory expectations are summarized. Criteria for immunological safety are addressed, including activation of innate immunity (complement, T- and NK-cell responses) and the need for HLA typing. Biodistribution assessment involves the use of quantitative PCR and imaging techniques (PET, MRI) to monitor cell fate over time. The risks of oncogenicity, tumorigenicity, and teratogenicity can be analyzed using a combination of in vitro methods and in vivo models in immunocompromised animals. Product quality assessment includes sterility, identity, potency, viability, and genetic stability, with alignment of procedures to regulatory requirements and an emphasis on quality-by-design principles to ensure safe and reproducible clinical use. Integrating toxicity and safety pharmacology data supports a balanced risk–benefit assessment and clinical trial planning. Full article
(This article belongs to the Special Issue Advances and Breakthroughs in Stem Cell Research)
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23 pages, 1461 KB  
Review
RNA Degradation in Pluripotent Stem Cells: Mechanisms, Crosstalk, and Fate Regulation
by Seunghwa Jeong, Myunggeun Oh, Jaeil Han and Seung-Kyoon Kim
Cells 2025, 14(20), 1634; https://doi.org/10.3390/cells14201634 - 20 Oct 2025
Viewed by 634
Abstract
Pluripotent stem cells (PSCs) exhibit remarkable self-renewal capacity and differentiation potential, necessitating tight regulation of gene expression at both transcriptional and post-transcriptional levels. Among post-transcriptional mechanisms, RNA turnover and degradation together play pivotal roles in maintaining transcriptome homeostasis and controlling RNA stability. RNA [...] Read more.
Pluripotent stem cells (PSCs) exhibit remarkable self-renewal capacity and differentiation potential, necessitating tight regulation of gene expression at both transcriptional and post-transcriptional levels. Among post-transcriptional mechanisms, RNA turnover and degradation together play pivotal roles in maintaining transcriptome homeostasis and controlling RNA stability. RNA degradation plays a pivotal role in determining transcript stability for both messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), thereby influencing cell identity and fate transitions. The core RNA decay machinery, which includes exonucleases, decapping complexes, RNA helicases, and the RNA exosome, ensures timely and selective decay of transcripts. In addition, RNA modifications such as 5′ capping and N6-methyladenosine (m6A) further modulate RNA stability, contributing to the fine-tuning of gene regulatory networks essential for maintaining PSC states. Recent single-cell and multi-omics studies have revealed that RNA degradation exhibits heterogeneous and dynamic kinetics during cell fate transitions, highlighting its role in preserving transcriptome homeostasis. Conversely, disruption of RNA decay pathways has been implicated in developmental defects and disease, underscoring their potential as therapeutic targets. Collectively, RNA degradation emerges as a central regulator of PSC biology, integrating the decay of both mRNAs and ncRNAs to orchestrate pluripotency maintenance, lineage commitment, and disease susceptibility. Full article
(This article belongs to the Special Issue Advances and Breakthroughs in Stem Cell Research)
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19 pages, 1967 KB  
Review
NSUN-Mediated m5C RNA Modification in Stem Cell Regulation
by Jiin Moon, Hyohi Lee, Yeonju Jang and Seung-Kyoon Kim
Cells 2025, 14(20), 1609; https://doi.org/10.3390/cells14201609 - 16 Oct 2025
Viewed by 590
Abstract
RNA modifications comprise a core epigenetic dimension of gene regulation; among these, N6-methyladenosine (m6A) and 5-methylcytosine (m5C) have been most intensively investigated. While the functions of m6A in stem cell biology have been well characterized, the contributions of m5C remain comparatively less well [...] Read more.
RNA modifications comprise a core epigenetic dimension of gene regulation; among these, N6-methyladenosine (m6A) and 5-methylcytosine (m5C) have been most intensively investigated. While the functions of m6A in stem cell biology have been well characterized, the contributions of m5C remain comparatively less well defined. This review focuses on m5C modifications catalyzed by the NSUN family of RNA methyltransferases and their roles in regulating stem cell identity, pluripotency, and differentiation. Evidence from embryonic and mesenchymal stem cells, as well as animal models, demonstrates that NSUN-mediated m5C is deposited on diverse RNA substrates, including rRNA, tRNA, mRNA, mitochondrial RNA, and enhancer RNAs, thereby influencing processes such as self-renewal, cell cycle progression, RNA stability, metabolic activation, and lineage specification. Disruption of m5C regulation often leads to developmental defects, underscoring its essential role during embryogenesis. Collectively, these findings establish m5C as a versatile and dynamic regulator in stem cell biology and underscore the need for future studies to delineate the roles of the NSUN family in stem cells and define the RNA targets of m5C. In addition, its broader implications for development, regenerative medicine, and disease, including cancer, as well as its potential interplay with other RNA modifications such as m6A and pseudouridine, remain important areas for further investigation. Full article
(This article belongs to the Special Issue Advances and Breakthroughs in Stem Cell Research)
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