Feature Papers in "Stem Cells" 2023

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

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 14107

Special Issue Editors


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Guest Editor
Center for Regenerative Biotherapeutics, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA
Interests: mesenchymal stem cells (MSC); MSC potentiation; MSC scale-up; regenerative medicine; immunomodulation; MSC signaling; clinical and translational research; process development

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Guest Editor
Department of Biology, University of Mary Hardin-Baylor, Belton, TX, USA
Interests: stem cells; mesenchymal stem cells; 3D culture; bioinformatics; immunology
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Special Issue Information

Dear Colleagues,

Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells hold great promise for future cell replacement therapies, with each having its pros and cons. The development of these stem cells requires in-depth knowledge in understanding and controlling the mechanisms of stem cell maintenance and exit from the undifferentiated state in specific biomaterials that mimick in vivo niches. When grown in 3D, ESCs or iPSCs can recapitulate embryonic development as blastoids or organoids do, making them ideal for drug screening and genetic disease modeling. Although cells of the inner cell mass are in a transient state in the embryo and last just for a few days, it has been possible to capture their pluripotent fate in vitro. Indeed, they can be grown as cell lines indefinitely thanks to deep insights in the fundamental knowledge of their physiology. Adult stem cells on the other hand last throughout our entire life in specific physiological niches in our body but can typically be cultured in vitro only through limited number of population doublings. In this Special issue of Cells, we will gather articles and reviews on recent fundamental and applied advances on ESC, iPSCs, and adult stem cells.

Dr. Nisha C. Durand
Dr. Joni H. Ylostalo
Guest Editors

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Published Papers (3 papers)

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Research

18 pages, 7351 KiB  
Article
Evaluating Differentiation Status of Mesenchymal Stem Cells by Label-Free Microscopy System and Machine Learning
by Yawei Kong, Jianpeng Ao, Qiushu Chen, Wenhua Su, Yinping Zhao, Yiyan Fei, Jiong Ma, Minbiao Ji and Lan Mi
Cells 2023, 12(11), 1524; https://doi.org/10.3390/cells12111524 - 31 May 2023
Cited by 2 | Viewed by 2516
Abstract
Mesenchymal stem cells (MSCs) play a crucial role in tissue engineering, as their differentiation status directly affects the quality of the final cultured tissue, which is critical to the success of transplantation therapy. Furthermore, the precise control of MSC differentiation is essential for [...] Read more.
Mesenchymal stem cells (MSCs) play a crucial role in tissue engineering, as their differentiation status directly affects the quality of the final cultured tissue, which is critical to the success of transplantation therapy. Furthermore, the precise control of MSC differentiation is essential for stem cell therapy in clinical settings, as low-purity stem cells can lead to tumorigenic problems. Therefore, to address the heterogeneity of MSCs during their differentiation into adipogenic or osteogenic lineages, numerous label-free microscopic images were acquired using fluorescence lifetime imaging microscopy (FLIM) and stimulated Raman scattering (SRS), and an automated evaluation model for the differentiation status of MSCs was built based on the K-means machine learning algorithm. The model is capable of highly sensitive analysis of individual cell differentiation status, so it has great potential for stem cell differentiation research. Full article
(This article belongs to the Special Issue Feature Papers in "Stem Cells" 2023)
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19 pages, 2902 KiB  
Article
High-Throughput Screening Assay for Detecting Drug-Induced Changes in Synchronized Neuronal Oscillations and Potential Seizure Risk Based on Ca2+ Fluorescence Measurements in Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neuronal 2D and 3D Cultures
by Hua-Rong Lu, Manabu Seo, Mohamed Kreir, Tetsuya Tanaka, Rie Yamoto, Cristina Altrocchi, Karel van Ammel, Fetene Tekle, Ly Pham, Xiang Yao, Ard Teisman and David J. Gallacher
Cells 2023, 12(6), 958; https://doi.org/10.3390/cells12060958 - 21 Mar 2023
Cited by 3 | Viewed by 6389
Abstract
Drug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence in late development results in increased costs, human risk, and delayed market availability of novel therapeutics. Therefore, there is an urgent need for biologically relevant, in [...] Read more.
Drug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence in late development results in increased costs, human risk, and delayed market availability of novel therapeutics. Therefore, there is an urgent need for biologically relevant, in vitro high-throughput screening assays (HTS) to predict potential risks for drug-induced seizure early in drug discovery. We investigated drug-induced changes in neural Ca2+ oscillations, using fluorescent dyes as a potential indicator of seizure risk, in hiPSC-derived neurons co-cultured with human primary astrocytes in both 2D and 3D forms. The dynamics of synchronized neuronal calcium oscillations were measured with an FDSS kinetics reader. Drug responses in synchronized Ca2+ oscillations were recorded in both 2D and 3D hiPSC-derived neuron/primary astrocyte co-cultures using positive controls (4-aminopyridine and kainic acid) and negative control (acetaminophen). Subsequently, blinded tests were carried out for 25 drugs with known clinical seizure incidence. Positive predictive value (accuracy) based on significant changes in the peak number of Ca2+ oscillations among 25 reference drugs was 91% in 2D vs. 45% in 3D hiPSC-neuron/primary astrocyte co-cultures. These data suggest that drugs that alter neuronal activity and may have potential risk for seizures can be identified with high accuracy using an HTS approach using the measurements of Ca2+ oscillations in hiPSC-derived neurons co-cultured with primary astrocytes in 2D. Full article
(This article belongs to the Special Issue Feature Papers in "Stem Cells" 2023)
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17 pages, 5459 KiB  
Article
Estrogen Signaling Influences Nephron Segmentation of the Zebrafish Embryonic Kidney
by Hannah M. Wesselman, Allison E. Gatz, Mairead R. Pfaff, Liana Arceri and Rebecca A. Wingert
Cells 2023, 12(4), 666; https://doi.org/10.3390/cells12040666 - 20 Feb 2023
Cited by 7 | Viewed by 2631
Abstract
Despite significant advances in understanding nephron segment patterning, many questions remain about the underlying genes and signaling pathways that orchestrate renal progenitor cell fate choices and regulate differentiation. In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput [...] Read more.
Despite significant advances in understanding nephron segment patterning, many questions remain about the underlying genes and signaling pathways that orchestrate renal progenitor cell fate choices and regulate differentiation. In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput drug screen using a bioactive chemical library and developing zebrafish, which are a conserved vertebrate model and particularly conducive to large-scale screening approaches. 17β-estradiol (E2), which is the dominant form of estrogen in vertebrates, was a particularly interesting hit from this screen. E2 has been extensively studied in the context of gonad development, but roles for E2 in nephron development were unknown. Here, we report that exogenous estrogen treatments affect distal tubule composition, namely, causing an increase in the distal early segment and a decrease in the neighboring distal late. These changes were noted early in development but were not due to changes in cell dynamics. Interestingly, exposure to the xenoestrogens ethinylestradiol and genistein yielded the same changes in distal segments. Further, upon treatment with an estrogen receptor 2 (Esr2) antagonist, PHTPP, we observed the opposite phenotypes. Similarly, genetic deficiency of the Esr2 analog, esr2b, revealed phenotypes consistent with that of PHTPP treatment. Inhibition of E2 signaling also resulted in decreased expression of essential distal transcription factors, irx3b and its target irx1a. These data suggest that estrogenic compounds are essential for distal segment fate during nephrogenesis in the zebrafish pronephros and expand our fundamental understanding of hormone function during kidney organogenesis. Full article
(This article belongs to the Special Issue Feature Papers in "Stem Cells" 2023)
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