HIF-Overexpression and Pro-Inflammatory Priming in Human Mesenchymal Stromal Cells Improves the Healing Properties of Extracellular Vesicles in Experimental Crohn’s Disease

Autor: Jesus Cosin-Roger, Maria Carmen Baquero, Maria D. Barrachina, Rafael Sánchez-Sánchez, Elena Amaro-Prellezo, Marta Gómez-Ferrer, Angeles Vicente, Pilar Sepúlveda, Jaris Valencia, Akaitz Dorronsoro
Rok vydání: 2021
Předmět:
Male
Crohn’s disease
medicine.medical_treatment
immunomodulation
Mice
Intestinal mucosa
Crohn Disease
Medicine
Biology (General)
Telomerase
Spectroscopy
Cell Polarity
General Medicine
Computer Science Applications
Chemistry
Cytokine
macrophage repolarization
hypoxia-inducible factor 1-alpha
Cytokines
mesenchymal stromal cells
Myofibroblast
Gastroenterología y hepatología
QH301-705.5
Catalysis
Article
Inorganic Chemistry
Extracellular Vesicles
Young Adult
Immune system
Cell Adhesion
Human Umbilical Vein Endothelial Cells
Animals
Humans
Physical and Theoretical Chemistry
Colitis
Efferocytosis
QD1-999
Molecular Biology
Acute colitis
business.industry
Organic Chemistry
Mesenchymal stem cell
Mesenchymal Stem Cells
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
Disease Models
Animal
Trinitrobenzenesulfonic Acid
Cancer research
business
Zdroj: E-Prints Complutense. Archivo Institucional de la UCM
instname
International Journal of Molecular Sciences
Volume 22
Issue 20
International Journal of Molecular Sciences, Vol 22, Iss 11269, p 11269 (2021)
Popis: Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have therapeutic potential in the treatment of several immune disorders, including ulcerative colitis, owing to their regenerative and immunosuppressive properties. We recently showed that MSCs engineered to overexpress hypoxia-inducible factor 1-alpha and telomerase (MSC-T-HIF) and conditioned with pro-inflammatory stimuli release EVs (EVMSC-T-HIFC) with potent immunomodulatory activity. We tested the efficacy of EVMSC-T-HIFC to repolarize M1 macrophages (Mφ1) to M2-like macrophages (Mφ2-like) by analyzing surface markers and cytokines and performing functional assays in co-culture, including efferocytosis and T-cell proliferation. We also studied the capacity of EVMSC-T-HIFC to dampen the inflammatory response of activated endothelium and modulate fibrosis. Finally, we tested the therapeutic capacity of EVMSC-T-HIFC in an acute colitis model. EVMSC-T-HIFc induced the repolarization of monocytes from Mφ1 to an Mφ2-like phenotype, which was accompanied by reduced inflammatory cytokine release. EVMSC-T-HIFc-treated Mφ1 had similar effects of immunosuppression on activated peripheral blood mononuclear cells (PBMC) as Mφ2, and reduced the adhesion of PBMCs to activated endothelium. EVMSC-T-HIFc also prevented myofibroblast differentiation of TGF-β-treated fibroblasts. Finally, administration of EVMSC-T-HIFc promoted healing in a TNBS-induced mouse colitis model in terms of preserving colon length and intestinal mucosa architecture and altering the ratio of Mφ1/ Mφ2 infiltration. In conclusion, EVMSC-T-HIFC have effective anti-inflammatory properties, making them potential therapeutic agents in cell free-based therapies for the treatment of Crohn’s disease and likely other immune-mediated inflammatory diseases.
Databáze: OpenAIRE
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