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Cells
Special Issues
Reprogrammed Cells in Disease Modeling and Drug Discovery
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Reprogrammed Cells in Disease Modeling and Drug Discovery

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 16558

Special Issue Editors

Prof. Xuefeng Liu

E-Mail Website
Guest Editor
Center for Cell Reprograming, Departments of Pathology and Oncology, Georgetown University Medical Center, Georgrtown, WA, 20057, USA
Interests: cell reprogramming; telomerase and telomeres; patient-derived models; cell therapies; living biobanks
Special Issues, Collections and Topics in MDPI journals
Dr. Andreas Kurtz

E-Mail Website
Guest Editor
BIH Center for Regenrative Therapies, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Interests: stem cells; cell data management, extracellular matrix; kidney organoids; regenerative medicine; ethics of organoids
Prof. Kyung Sun Kang

E-Mail Website
Guest Editor
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
Interests: stem cell therapy; organoid; reprograming and direct conversion; universial stem cells

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% 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 widely used 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, 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. Xuefeng Liu,
Prof. Andreas Kurtz,
Prof. Kyung Sun Kang,
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

  • patient-derived cells
  • iPS (induced pluripotent stem cells)
  • CRC (conditionally reprogrammed cells)
  • organoids
  • human diseases
  • disease modeling
  • cancer models
  • drug discovery

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Published Papers (3 papers)

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Research

18 pages, 7594 KiB  
Article
Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids
by Min Soo Kim, Da-Hyun Kim, Hyun Kyoung Kang, Myung Geun Kook, Soon Won Choi and Kyung-Sun Kang
Cells 2021, 10(2), 234; https://doi.org/10.3390/cells10020234 - 25 Jan 2021
Cited by 23 | Viewed by 5663
Abstract
Brain organoids have emerged as a novel model system for neural development, neurodegenerative diseases, and human-based drug screening. However, the heterogeneous nature and immature neuronal development of brain organoids generated from pluripotent stem cells pose challenges. Moreover, there are no previous reports of [...] Read more.
Brain organoids have emerged as a novel model system for neural development, neurodegenerative diseases, and human-based drug screening. However, the heterogeneous nature and immature neuronal development of brain organoids generated from pluripotent stem cells pose challenges. Moreover, there are no previous reports of a three-dimensional (3D) hypoxic brain injury model generated from neural stem cells. Here, we generated self-organized 3D human neural organoids from adult dermal fibroblast-derived neural stem cells. Radial glial cells in these human neural organoids exhibited characteristics of the human cerebral cortex trend, including an inner (ventricular zone) and an outer layer (early and late cortical plate zones). These data suggest that neural organoids reflect the distinctive radial organization of the human cerebral cortex and allow for the study of neuronal proliferation and maturation. To utilize this 3D model, we subjected our neural organoids to hypoxic injury. We investigated neuronal damage and regeneration after hypoxic injury and reoxygenation. Interestingly, after hypoxic injury, reoxygenation restored neuronal cell proliferation but not neuronal maturation. This study suggests that human neural organoids generated from neural stem cells provide new opportunities for the development of drug screening platforms and personalized modeling of neurodegenerative diseases, including hypoxic brain injury. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery)
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14 pages, 7753 KiB  
Communication
Conditionally Reprogrammed Cells from Patient-Derived Xenograft to Model Neuroendocrine Prostate Cancer Development
by Xinpei Ci, Jun Hao, Xin Dong, Hui Xue, Rebecca Wu, Stephen Yiu Chuen Choi, Anne M. Haegert, Colin C. Collins, Xuefeng Liu, Dong Lin and Yuzhuo Wang
Cells 2020, 9(6), 1398; https://doi.org/10.3390/cells9061398 - 4 Jun 2020
Cited by 16 | Viewed by 3804
Abstract
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It develops mainly via NE transdifferentiation of prostate adenocarcinoma in response to androgen receptor (AR)-inhibition therapy. The study of NEPC development has been hampered by a lack of clinically relevant models. We [...] Read more.
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It develops mainly via NE transdifferentiation of prostate adenocarcinoma in response to androgen receptor (AR)-inhibition therapy. The study of NEPC development has been hampered by a lack of clinically relevant models. We previously established a unique and first-in-field patient-derived xenograft (PDX) model of adenocarcinoma (LTL331)-to-NEPC (LTL331R) transdifferentiation. In this study, we applied conditional reprogramming (CR) culture to establish a LTL331 PDX-derived cancer cell line named LTL331_CR_Cell. These cells retain the same genomic mutations as the LTL331 parental tumor. They can be continuously propagated in vitro and can be genetically manipulated. Androgen deprivation treatment on LTL331_CR_Cells had no effect on cell proliferation. Transcriptomic analyses comparing the LTL331_CR_Cell to its parental tumor revealed a profound downregulation of the androgen response pathway and an upregulation of stem and basal cell marker genes. The transcriptome of LTL331_CR_Cells partially resembles that of post-castrated LTL331 xenografts in mice. Notably, when grafted under the renal capsules of male NOD/SCID mice, LTL331_CR_Cells spontaneously gave rise to NEPC tumors. This is evidenced by the histological expression of the NE marker CD56 and the loss of adenocarcinoma markers such as PSA. Transcriptomic analyses of the newly developed NEPC tumors further demonstrate marked enrichment of NEPC signature genes and loss of AR signaling genes. This study provides a novel research tool derived from a unique PDX model. It allows for the investigation of mechanisms underlying NEPC development by enabling gene manipulations ex vivo and subsequent functional evaluations in vivo. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery)
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12 pages, 2382 KiB  
Article
Fabrication of Dentin-Pulp-Like Organoids Using Dental-Pulp Stem Cells
by Sang Yun Jeong, Soonchul Lee, Woo Hee Choi, Joo Hyun Jee, Hyung-Ryong Kim and Jongman Yoo
Cells 2020, 9(3), 642; https://doi.org/10.3390/cells9030642 - 6 Mar 2020
Cited by 30 | Viewed by 6266
Abstract
We developed a novel dentin-pulp-like organoid. It has both stem-cell and odontoblast characteristics using a mesenchymal cell lineage of human dental-pulp stem cells (hDPSCs). The mixture of hDPSCs and Matrigel was transferred into the maintenance medium (MM) and divided into four different groups [...] Read more.
We developed a novel dentin-pulp-like organoid. It has both stem-cell and odontoblast characteristics using a mesenchymal cell lineage of human dental-pulp stem cells (hDPSCs). The mixture of hDPSCs and Matrigel was transferred into the maintenance medium (MM) and divided into four different groups according to how long they were maintained in the odontogenic differentiation medium (ODM). All organoids were harvested at 21 days and analyzed to find the optimal differentiation condition. To assess the re-fabrication of dentin-pulp-like organoid, after dissociation of the organoids, it was successfully regenerated. Additionally, its biological activity was confirmed by analyzing changes of relevant gene expression and performing a histology analysis after adding Biodentine® into the ODM. The organoid was cultured for 11 days in the ODM (ODM 11) had the most features of both stem cells and differentiated cells (odontoblasts) as confirmed by relevant gene expression and histology analyses. Micro-computed tomography and an electron microscope also showed mineralization and odontoblastic differentiation. Finally, ODM 11 demonstrated a biologically active response to Biodentine® treatment. In conclusion, for the first time, we report the fabrication of a dentin-pulp-like organoid using mesenchymal stem cells. This organoid has potential as a future therapeutic strategy for tooth regeneration. Full article
(This article belongs to the Special Issue Reprogrammed Cells in Disease Modeling and Drug Discovery)
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