Stem Cells and Organoids as Tools for Drug Development

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 1315

Special Issue Editor


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Guest Editor
Institute of Biostructures and Bioimaging, National Research Council, IBB-CNR, 80145 Naples, Italy
Interests: embryonic stem cells (ESCs); ESC self-renewal and differentiation; mouse models; embryo development; metabolism; toxicity screening; disease modeling

Special Issue Information

Dear Colleagues,

In the last 20 years, pharmaceutical development and evaluation costs have increased dramatically. Numerous failed clinical trials indicate that drug development and testing procedures in animal models and standard cell lines are not reliably predictive for human efficacy and safety.

Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) can be propagated extensively in vitro while retaining the ability to differentiate into any specialized cell type within the body; these unique features of hPSCs offer a way of producing relevant in vitro models amenable to high-throughput testing for drug discovery. Moreover, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies, but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease.

In the last decade, organoid technology, an innovative three-dimensional (3D) model, has risen rapidly and become increasingly prevalent among researchers. Organoids are 3D tissues in miniature in vitro (established from ESCs, iPSCs, and tumor cells), which are specific to the parent counterparts in vivo. Organoid technology demonstrates tremendous potential for clinical applications. Firstly, organoids can be exploited as an excellent platform to evaluate drug efficacy and toxicity, ultimately promoting drug development. Secondly, precision medicine may represent another pivotal branch of organoid technology by accurately predicting drug responses and guiding optimized treatment strategies for each individual patient.

This Special Issue will provide an opportunity to discuss the application of stem cells and organoids from healthy and diseased sources in drug screening and their role in complementing, reducing, and replacing animal trials. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells will also be focused on. We welcome articles that deal with all aspects of pharmaceutical and medical care, from basic to clinical research, and invite scientists to publish their original research works, review articles, and communications on this wide health domain.

Dr. Daniela Omodei
Guest Editor

Manuscript Submission Information

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Keywords

  • stem cells
  • patient-derived cells
  • iPSCs (induced pluripotent stem cells)
  • organoids
  • drug development
  • drug screening
  • drug toxicity
  • preclinical and clinical drug research
  • novel therapeutics
  • disease modeling
  • personalized medicine
  • precision medicine

Published Papers (1 paper)

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Research

12 pages, 1730 KiB  
Article
Oxaliplatin Enhances the Apoptotic Effect of Mesenchymal Stem Cells, Delivering Soluble TRAIL in Chemoresistant Colorectal Cancer
by Adriana G Quiroz-Reyes, Paulina Delgado-González, José F. Islas, Adolfo Soto-Domínguez, Carlos A. González-Villarreal, Gerardo R. Padilla-Rivas and Elsa N. Garza-Treviño
Pharmaceuticals 2023, 16(10), 1448; https://doi.org/10.3390/ph16101448 - 12 Oct 2023
Viewed by 1035
Abstract
A key problem in colorectal cancer (CRC) is the development of resistance to current therapies due to the presence of cancer stem cells (CSC), which leads to poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that activates apoptosis in cancer [...] Read more.
A key problem in colorectal cancer (CRC) is the development of resistance to current therapies due to the presence of cancer stem cells (CSC), which leads to poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that activates apoptosis in cancer cells through union with TRAIL death receptors. Cell therapies as delivery systems can produce soluble TRAIL (sTRAIL) and full-length TRAIL (flTRAIL), showing a high capacity to produce apoptosis in vitro and in vivo assays. However, the apoptotic activity of TRAIL as monotherapy had limitations, so it is important to explore other ways to enhance susceptibility to TRAIL. This study evaluated the cytotoxic and proapoptotic activity of soluble TRAIL overexpressed by mesenchymal stem cells (MSC) in an oxaliplatin-resistant CRC cell line. Bone marrow-MSC were lentiviral transduced for soluble TRAIL expression. DR5 death receptor expression was determined in Caco-2 and CMT-93 CRC cell lines. Sensitivity to first-line chemotherapies and recombinant TRAIL was evaluated by half-maximal inhibitory concentrations. Cytotoxic and proapoptotic activity of soluble TRAIL-MSC alone and combined with chemotherapy pre-treatment was evaluated using co-cultures. Caco-2 and CMT-93 cell lines expressed 59.08 ± 5.071 and 51.65 ± 11.99 of DR5 receptor and had IC50 of 534.15 ng/mL and 581.34 ng/mL for recombinant murine TRAIL (rmTRAIL), respectively. This finding was classified as moderate resistance to TRAIL. The Caco-2 cell line showed resistance to oxaliplatin and irinotecan. MSC successfully overexpressed soluble TRAIL and induced cancer cell death at a 1:6 ratio in co-culture. Oxaliplatin pre-treatment in the Caco-2 cell line increased the cell death percentage (50%) and apoptosis by sTRAIL. This finding was statistically different from the negative control (p < 0.05), and activity was even higher with the oxaliplatin–flTRAIL combination. Thus, oxaliplatin increases apoptotic activity induced by soluble TRAIL in a chemoresistant CRC cell line. Full article
(This article belongs to the Special Issue Stem Cells and Organoids as Tools for Drug Development)
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