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The Roles of Mesenchymal Stem/Stromal Cells in Tumor Therapies

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Guest Editor
Stem Cell Unit, Department of Research and Advanced Cancer Diagnostic, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
Interests: mesenchymal stem cells; cancer; drug delivery; good manufacturing practice; cell therapy; medium additive substitutes; microfluidic conditions; homing; migration; gene editing by non-viral methods

Special Issue Information

Dear Colleagues,

Mesenchymal stem/stromal cells (MSCs) have been extensively studied because they can be used as advanced therapy medicinal products (ATMPs). MSCs can be applied in oncology to counteract graft-versus-host disease and as drug delivery vehicles against cancer. MSCs are characterized by the capacity to home into the cancer microenvironment. Evidence from clinical trials was encouraging because product safety was demonstrated, but results regarding MSC-mediated cancer regression were not completely satisfactory. Naïve MSCs can play regenerative roles for neighboring cells and this could promote tumor growth. Therefore, procedures are required to induce in MSCs a clear cytotoxic behavior against cancer cells. Moreover, the amount of infused MSCs homing into the cancer mass is limited; thus, strategies are needed to improve such MSC capacity. The implementation of these and other ways to ameliorate MSC properties will reasonably provide effective cell products for cancer care.

The present Special Issue will accept papers focused on MSCs as tools to ameliorate cancer patient prognosis using results obtained in vitro, in vivo and clinical trials. Innovative cancer research on cell-free therapeutic products (exosomes or microvesicles), and submissions considering compliance with guidelines for the clinical-grade manufacturing of ATMPs will be welcome.

Dr. Francesco Agostini
Guest Editor

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Keywords

  • mesenchymal stem cells
  • tumor
  • cancer patients
  • ex vivo cell modification
  • cell and gene therapy
  • targeted drug delivery
  • homing
  • migration
  • current regulatory guidelines
  • MSC therapeutic potential

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Published Papers (1 paper)

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Research

28 pages, 7774 KiB  
Article
Chemoresistance in Pancreatic Cancer: The Role of Adipose-Derived Mesenchymal Stem Cells and Key Resistance Genes
by Shahram Parvaneh, Vanda Miklós, Zoltán Gábor Páhi, Diána Szűcs, Tamás Monostori, Szilárd Póliska, Viktória Venglovecz, Tibor Pankotai, Lajos Kemény and Zoltán Veréb
Int. J. Mol. Sci. 2025, 26(1), 390; https://doi.org/10.3390/ijms26010390 - 4 Jan 2025
Viewed by 1104
Abstract
Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) [...] Read more.
Drug resistance is a significant challenge in pancreatic ductal adenocarcinoma (PDAC), where stromal elements such as adipose-derived mesenchymal stem cells (ASCs) contribute to a chemoresistant tumor microenvironment (TME). This study explored the effects of oxaliplatin (OXP) and 5-fluorouracil (5-FU) on PDAC cells (Capan-1) and ASCs to investigate the mechanisms of chemoresistance. While OXP and 5-FU reduced Capan-1 viability in a dose- and time-dependent manner, ASCs demonstrated high resistance, maintaining > 90% viability even at cytotoxic doses. Transcriptomic analyses revealed OXP-induced transcriptional reprogramming in ASCs, with over 7000 differentially expressed genes, highlighting the pathways related to DNA damage response, cell cycle regulation, and stress-related signaling. In contrast, 5-FU elicited limited transcriptional changes, affecting only 192 genes. Cytokine proteome profiling revealed that OXP-treated ASCs significantly influenced the tumor microenvironment by promoting immune evasion (via IL-4, GM-CSF, IP-10, and GROα) and driving extracellular matrix remodeling (through EMMPRIN and DPPIV). In contrast, 5-FU induced comparatively weaker effects, primarily limited to hypoxia-related pathways. Although OXP reduced angiogenic factors, it paradoxically activated pro-survival pathways, thereby enhancing ASC-mediated tumor support. These findings underscore ASCs as modulators of chemoresistance via secretome alterations and stress adaptation. Therefore, future strategies should prioritize the precise targeting of tumor cells while also focusing on the development of personalized treatments to achieve durable therapeutic responses in PDAC. Full article
(This article belongs to the Special Issue The Roles of Mesenchymal Stem/Stromal Cells in Tumor Therapies)
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