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Cells
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Reprogrammed Cells in Disease Modeling and Drug Discovery II
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Reprogrammed Cells in Disease Modeling and Drug Discovery II

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: 20 June 2024 | Viewed by 9524

Special Issue Editor

Prof. Dr. Xuefeng Liu

E-Mail Website1 Website2
Guest Editor
1. Center for Cell Reprograming, Departments of Pathology and Oncology, Georgetown University Medical Center, Georgrtown, WA, 20057, USA
2. Departments of Pathology and Urology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
Interests: cell reprogramming; telomerase and telomeres; patient-derived models; cell therapies; living biobanks; viruses; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Traditional cancer models, including cell lines and animal models, have been widely used but have seen limited applications in both basic and clinical cancer research. Patient-derived model systems are needed for modeling human diseases and precision medicine. Genomics-based precision oncology only helps 2-20% of patients with solid cancer, and as such, functional diagnostics and patient-derived models are needed for precision cancer biology. Induced pluripotent stem cells (iPS), organoids, and conditional reprogramming (CR) are currently used widely for patient-derived cell models for disease and precision medicine. Both organoids and CR technologies have been cited in two NCI programs—PDMR (patient-derived cancer model repository) and HCMI (human cancer model initiatives), the latter of which will be distributed through ATCC. These cells can be easily manipulated in vitro, and thus, these patient-derived cells could be used for next-generation disease models. In this Special Issue, we will focus on the applications of cell reprogramming technologies (including iPS, CR, organoids, and others) in disease modeling including cancer, inflammatory, genetic diseases, infectious diseases (virus infection models), and drug discovery.

Prof. Dr. Xuefeng Liu
Guest Editor

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

  • patient-derived cells
  • iPS (induced pluripotent stem cells)
  • CRC (conditionally reprogrammed cells)
  • organoids
  • air–liquid interface cultures
  • circulating tumor cells
  • human diseases
  • disease modeling
  • cancer models
  • drug discovery

Published Papers (5 papers)

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Research

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16 pages, 4671 KiB  
Article
CRC Therapy Identifies Indian Hedgehog Signaling in Mouse Endometrial Epithelial Cells and Inhibition of Ihh-KLF9 as a Novel Strategy for Treating IUA
by Xinhao Zhou, Yiyi Kang, Yuntzu Chang, Siyu Xia, Ming Wu, Jun Liu, Dirong Dong, Wei Zhang, Hong Chen and Hui Li
Cells 2022, 11(24), 4053; https://doi.org/10.3390/cells11244053 - 15 Dec 2022
Viewed by 1574
Abstract
Intrauterine adhesion (IUA) causes menstrual disturbance and infertility. There is no effective treatment available for moderate to severe IUA cases. Stem cell-based therapy has been investigated for treating IUA but is limited in clinical applications due to issues including the precise induction of [...] Read more.
Intrauterine adhesion (IUA) causes menstrual disturbance and infertility. There is no effective treatment available for moderate to severe IUA cases. Stem cell-based therapy has been investigated for treating IUA but is limited in clinical applications due to issues including the precise induction of differentiation, tumorigenesis, and unclear molecular mechanisms. In our recent study, we isolated and expanded the long-term cultures of conditional reprogrammed (CR) mouse endometrial epithelial cells. Treating IUA mice with these CR cells (CRCs) restored the morphology and structure of the endometrium and significantly improved the pregnancy rate. In this study, our data with high-throughput sequencing, CRISPR knockout Ihh−/−CRCs, and transplantation identified for the first time that the Indian hedgehog (Ihh) gene plays a critical role in the regulation of endometrial epithelial cell proliferation. We also found that aberrant activated Ihh-krüppel-like factor 9 (KLF9) signaling contributes to the inhibition of normal progesterone receptor (PR) function in IUA mice. Thus, we hypothesized that inhibition of the Ihh-KLF9 pathway may be a novel strategy to treat IUA. Our data demonstrated that treatment with the hedgehog signaling inhibitor Vismodegib restored the morphology, structure, and microenvironment of the endometrium, and greatly improved the pregnancy rate in IUA mice. This study suggests a promising application of hedgehog inhibitors as a targeted drug in the IUA clinic. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery II)
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Review

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22 pages, 1104 KiB  
Review
Interconversion of Cancer Cells and Induced Pluripotent Stem Cells
by Drishty B. Sarker, Yu Xue, Faiza Mahmud, Jonathan A. Jocelyn and Qing-Xiang Amy Sang
Cells 2024, 13(2), 125; https://doi.org/10.3390/cells13020125 - 10 Jan 2024
Cited by 1 | Viewed by 1581
Abstract
Cancer cells, especially cancer stem cells (CSCs), share many molecular features with induced pluripotent stem cells (iPSCs) that enable the derivation of induced pluripotent cancer cells by reprogramming malignant cells. Conversely, normal iPSCs can be converted into cancer stem-like cells with the help [...] Read more.
Cancer cells, especially cancer stem cells (CSCs), share many molecular features with induced pluripotent stem cells (iPSCs) that enable the derivation of induced pluripotent cancer cells by reprogramming malignant cells. Conversely, normal iPSCs can be converted into cancer stem-like cells with the help of tumor microenvironment components and genetic manipulation. These CSC models can be utilized in oncogenic initiation and progression studies, understanding drug resistance, and developing novel therapeutic strategies. This review summarizes the role of pluripotency factors in the stemness, tumorigenicity, and therapeutic resistance of cancer cells. Different methods to obtain iPSC-derived CSC models are described with an emphasis on exposure-based approaches. Culture in cancer cell-conditioned media or cocultures with cancer cells can convert normal iPSCs into cancer stem-like cells, aiding the examination of processes of oncogenesis. We further explored the potential of reprogramming cancer cells into cancer-iPSCs for mechanistic studies and cancer dependencies. The contributions of genetic, epigenetic, and tumor microenvironment factors can be evaluated using these models. Overall, integrating iPSC technology into cancer stem cell research holds significant promise for advancing our knowledge of cancer biology and accelerating the development of innovative and tailored therapeutic interventions. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery II)
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Graphical abstract

14 pages, 866 KiB  
Review
Conditional Reprogramming Modeling of Bladder Cancer for Clinical Translation
by Danyal Daneshdoust, Ming Yin, Mingjue Luo, Debasish Sundi, Yongjun Dang, Cheryl Lee, Jenny Li and Xuefeng Liu
Cells 2023, 12(13), 1714; https://doi.org/10.3390/cells12131714 - 24 Jun 2023
Cited by 1 | Viewed by 1908
Abstract
The use of advanced preclinical models has become increasingly important in drug development. This is particularly relevant in bladder cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select [...] Read more.
The use of advanced preclinical models has become increasingly important in drug development. This is particularly relevant in bladder cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (chemotherapy, radiotherapy, immunotherapy, and/or surgery) are largely absent. Patient-derived and clinically relevant models including patient-derived xenografts (PDX), organoids, and conditional reprogramming (CR) of cell cultures efficiently generate numerous models and are being used in both basic and translational cancer biology. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have utilized CR technology to conduct bladder cancer research. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery II)
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10 pages, 553 KiB  
Review
Mesenchymal Stem Cells in Radiation-Induced Pulmonary Fibrosis: Future Prospects
by Yusha Chen, Xuefeng Liu and Zhaohui Tong
Cells 2023, 12(1), 6; https://doi.org/10.3390/cells12010006 - 20 Dec 2022
Cited by 5 | Viewed by 1656
Abstract
Radiation-induced pulmonary fibrosis (RIPF) is a general and fatal side effect of radiotherapy, while the pathogenesis has not been entirely understood yet. By now, there is still no effective clinical intervention available for treatment of RIPF. Recent studies revealed mesenchymal stromal cells (MSCs) [...] Read more.
Radiation-induced pulmonary fibrosis (RIPF) is a general and fatal side effect of radiotherapy, while the pathogenesis has not been entirely understood yet. By now, there is still no effective clinical intervention available for treatment of RIPF. Recent studies revealed mesenchymal stromal cells (MSCs) as a promising therapy treatment due to their homing and differentiation ability, paracrine effects, immunomodulatory effects, and MSCs-derived exosomes. Nevertheless, problems and challenges in applying MSCs still need to be taken seriously. Herein, we reviewed the mechanisms and challenges in the applications of MSCs in treating RIPF. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery II)
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12 pages, 1084 KiB  
Review
Translation Potential and Challenges of In Vitro and Murine Models in Cancer Clinic
by Yuan Long, Bin Xie, Hong C. Shen and Danyi Wen
Cells 2022, 11(23), 3868; https://doi.org/10.3390/cells11233868 - 30 Nov 2022
Cited by 4 | Viewed by 1815
Abstract
As one of the leading causes of death from disease, cancer continues to pose a serious threat to human health globally. Despite the development of novel therapeutic regimens and drugs, the long-term survival of cancer patients is still very low, especially for those [...] Read more.
As one of the leading causes of death from disease, cancer continues to pose a serious threat to human health globally. Despite the development of novel therapeutic regimens and drugs, the long-term survival of cancer patients is still very low, especially for those whose diagnosis is not caught early enough. Meanwhile, our understanding of tumorigenesis is still limited. Suitable research models are essential tools for exploring cancer mechanisms and treatments. Herein we review and compare several widely used in vitro and in vivo murine cancer models, including syngeneic tumor models, genetically engineered mouse models (GEMM), cell line-derived xenografts (CDX), patient-derived xenografts (PDX), conditionally reprogrammed (CR) cells, organoids, and MiniPDX. We will summarize the methodology and feasibility of various models in terms of their advantages and limitations in the application prospects for drug discovery and development and precision medicine. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery II)
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