Induced pluripotent stem cell (iPSC)-derived mesenchymal stromal cells (iMSCs) offer a promising alternative to primary mesenchymal stromal cells (MSCs) and their derivatives, particularly extracellular vesicles (EVs), for use in advanced therapy medicinal products. In this study we evaluated the immunomodulatory and regenerative potential of iMSCs as well as iMSC-EVs, alongside primary human umbilical cord-derived mesenchymal stromal cells (hUCMSCs). Our findings demonstrate that iMSCs exhibit comparable abilities to hUCMSCs in regulating lymphocyte proliferation and inducing an anti-inflammatory phenotype in monocytes. We also observed decreased TNFα levels and increased IL-10 induction, indicating a potential mechanism for their immunomodulatory effects. Furthermore, iMSC-EVs also showed effective immunomodulation by inhibiting T cell proliferation and inducing macrophage polarization similar to their parental cells. Additionally, iMSC-EVs exhibited pro-regenerative potential akin to hUCMSC-EVs in in vitro scratch assays. Notably, priming iMSCs with pro-inflammatory cytokines significantly enhanced the immunomodulatory potential of iMSC-EVs. These results underscore the considerable promise of iMSCs and iMSCs-EVs as an alternate source for MSC-derived therapeutics, given their potent immunomodulatory and regenerative properties.
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http://dx.doi.org/10.1038/s41598-024-75956-3 | DOI Listing |
J Med Chem
January 2025
Department of Chemistry and Chemical Biology, TU Dortmund University and Drug Discovery Hub Dortmund (DDHD), Zentrum für Integrierte Wirkstoffforschung (ZIW), Otto-Hahn-Strasse 4a, Dortmund 44227, Germany.
Gastrointestinal stromal tumors (GIST), driven by KIT and PDGFRA mutations, are the most common mesenchymal tumors of the gastrointestinal tract. Although tyrosine kinase inhibitors (TKIs) have advanced treatment, resistance mutations and off-target toxicity limit their efficacy. This study develops covalent TKIs targeting drug-resistant GIST through structure-based design, synthesis, and biological evaluation.
View Article and Find Full Text PDFMyelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs).
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Guangming District, Shenzhen, Guangdong, 518107, China.
Cancer-associated fibroblasts (CAFs) are crucial stromal cells in the tumor microenvironment, affecting cancer growth, angiogenesis, and matrix remodeling. Developing an effective in vitro tumor model that accurately recapitulates the dynamic interplay between tumor and stromal cells remains a challenge. In this study, a 3D bioprinted fibroblast - mediated heterogeneous breast tumor model was created, with tumor cells and fibroblasts in a bionic matrix.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Critical Care Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China.
Sepsis-induced acute lung injury (ALI) remains a leading cause of mortality in critically ill patients. Macrophages, key modulators of immune responses, play a dual role in both promoting and resolving inflammation. Exosomes, small extracellular vesicles released by various cells, carry bioactive molecules that influence macrophage polarization and immune responses.
View Article and Find Full Text PDFFront Oncol
January 2025
Department of Gastroenterology, Shengli Oilfield Central Hospital, Dongying, China.
Introduction: Gastric glomus tumor is a rare submucosal mesenchymal tumor with no distinct features on endoscopy. In clinical practice, it is often treated with laparoscopic partial gastrectomy. Here, we report a case of gastric glomus tumor successfully resected using a combination of gastroscopy and laparoscopy.
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