ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/049/SRR15017349/SRR15017349_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/051/SRR15017351/SRR15017351_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/047/SRR15017347/SRR15017347_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/045/SRR15017345/SRR15017345_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/048/SRR15017348/SRR15017348_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/043/SRR15017343/SRR15017343_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/051/SRR15017351/SRR15017351_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/046/SRR15017346/SRR15017346_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/052/SRR15017352/SRR15017352_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/045/SRR15017345/SRR15017345_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/048/SRR15017348/SRR15017348_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/044/SRR15017344/SRR15017344_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/050/SRR15017350/SRR15017350_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/052/SRR15017352/SRR15017352_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/044/SRR15017344/SRR15017344_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/049/SRR15017349/SRR15017349_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/047/SRR15017347/SRR15017347_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/050/SRR15017350/SRR15017350_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/046/SRR15017346/SRR15017346_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR150/043/SRR15017343/SRR15017343_1.fastq.gzprimaryOK200GenomicsDIvision of Molecular Oncology, Graduate School of Medicine, Nagoya Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA743094Rattus norvegicusxref:PubMed:35902687Adipose-derived mesenchymal stem cells (ASCs) have shown therapeutic potentials against refractory diseases. However, the detailed therapeutic mechanisms remain unclear. Here, we report the therapeutic actions of human ASCs in nephritis, focusing on cellular dynamics and multi-organ networks. Intravenously-administered ASCs accumulated in spleen but not kidneys. Nevertheless, ASCs increased M2 macrophages and Tregs in kidneys and drove strong renoprotection. Splenectomy abolished these therapeutic effects. ASC-derived extracellular vesicles (EVs) were transferred to M2 macrophages, which entered the bloodstream from spleen. EVs induced the transcriptomic signatures of hyperpolarization and PGE2 stimulation in M2 macrophages and ameliorated glomerulonephritis. ASCs, ASC-derived EVs, and EV-transferred M2 macrophages enhanced Treg induction. These findings suggest that EV transfer from spleen-accumulated ASCs to M2 macrophages and subsequent modulation of renal immune-environment underlie the renoprotective effects of ASCs. Our results provide new insights into the therapeutic actions of ASCs, focusing on EV-mediated modulation of macrophages and the spleen-kidney immune network. Overall design: RNA sequencing (RNA-seq) to study the impacts of ASCs-derived EVs on M2 macrophages in a rat nephritis model.ENAMultipotent Bone Marrow Stromal Cells, Mesenchymal Stem Cell, Adipose-Derived Mesenchymal Stem Cell, Exovesicles, Apoptotic Body, Bodies, Monocyte Derived Macrophages, Mesenchymal Stem Cells, Progenitor Cells, Stem Cells, Apoptotic Bodies, Progenitor Cell, Stromal Cells, Vesicles, Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stromal Cell, Mesenchymal Progenitor Cells, Wharton's Jelly Cells, Multipotent Mesenchymal Stromal Cell, Extracellular Vesicle, Monocyte Derived, Adipose Tissue-Derived Mesenchymal Stem Cell, microparticle, Vesicle, Monocyte-Derived, Mesenchymal Stromal Cell, Stem Cell, Stromal Cell, Apoptotic, Monocyte-Derived Macrophage, Wharton Jelly Cells, Wharton's Jelly Cell, Exovesicle, Monocyte-Derived Macrophages, Multipotent Mesenchymal Stromal Cells, Macrophage, Adipose Tissue-Derived Mesenchymal Stromal Cells, Bone Marrow Stromal Cell, Adipose Derived Mesenchymal Stem Cells, Adipose-Derived, Adipose-Derived Mesenchymal Stem Cells, reniculate kidney., Adipose Tissue Derived Mesenchymal Stromal Cells, Macrophages, Multipotent Bone Marrow Stromal Cell, Adipose Tissue-Derived Mesenchymal Stromal Cell, lien, Bone Marrow Derived Macrophages, Bone Marrow Stromal Stem Cells, Bone Marrow-Derived Macrophage, Adipose Tissue Derived Mesenchymal Stem Cells, Body, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, Bone Marrow-Derived, Bone Marrow Mesenchymal Stem Cells, Kidneys, Adipose Tissue-Derived Mesenchymal Stem Cells, Mesenchymal Progenitor Cell, Whartons Jelly Cells, Extracellular, Multipotent, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Bone Marrow-Derived Macrophages, Adipose Tissue Derived Mesenchymal Stem Cell, Bone Marrow Stromal Cells, Bone Marrow Mesenchymal Stem Cell, Adipose Derived Mesenchymal Stem CellMultipotent Bone Marrow Stromal Cells, Mesenchymal Stem Cell, Adipose-Derived Mesenchymal Stem Cell, Exovesicles, Apoptotic Body, Bodies, Monocyte Derived Macrophages, Mesenchymal Stem Cells, Progenitor Cells, Stem Cells, Apoptotic Bodies, Progenitor Cell, Stromal Cells, Vesicles, Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stromal Cell, Mesenchymal Progenitor Cells, Wharton's Jelly Cells, Multipotent Mesenchymal Stromal Cell, Extracellular Vesicle, Monocyte Derived, Adipose Tissue-Derived Mesenchymal Stem Cell, microparticle, Vesicle, Monocyte-Derived, Mesenchymal Stromal Cell, Stem Cell, Stromal Cell, Apoptotic, Monocyte-Derived Macrophage, Wharton Jelly Cells, Wharton's Jelly Cell, Exovesicle, Monocyte-Derived Macrophages, Multipotent Mesenchymal Stromal Cells, Macrophage, Adipose Tissue-Derived Mesenchymal Stromal Cells, Bone Marrow Stromal Cell, Adipose Derived Mesenchymal Stem Cells, Adipose-Derived, Adipose-Derived Mesenchymal Stem Cells, reniculate kidney., Adipose Tissue Derived Mesenchymal Stromal Cells, Macrophages, Multipotent Bone Marrow Stromal Cell, Adipose Tissue-Derived Mesenchymal Stromal Cell, lien, Bone Marrow Derived Macrophages, Bone Marrow Stromal Stem Cells, Bone Marrow-Derived Macrophage, Adipose Tissue Derived Mesenchymal Stem Cells, Body, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, Bone Marrow-Derived, Bone Marrow Mesenchymal Stem Cells, Kidneys, Adipose Tissue-Derived Mesenchymal Stem Cells, Mesenchymal Progenitor Cell, Whartons Jelly Cells, Extracellular, Multipotent, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Bone Marrow-Derived Macrophages, Adipose Tissue Derived Mesenchymal Stem Cell, Bone Marrow Stromal Cells, Bone Marrow Mesenchymal Stem Cell, Adipose Derived Mesenchymal Stem CellfalseMesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network.Mesenchymal stem cells exert renoprotection via extracellular vesicle-mediated modulation of M2 macrophages and spleen-kidney network.2025-09-242022-06-23PRJNA743094GSE1793011011635902687