Extracellular Vesicles from MSC Modulate the Immune Response to Renal Allografts in a MHC Disparate Rat Model

Stem Cells International
M KochC Lange

Abstract

Application of mesenchymal stromal cells (MSC) has been proposed for solid organ transplantation based on their potent immunomodulatory effects. Since side effects from the injection of large cells cannot be excluded, the hypothesis rises that extracellular vesicles (EV) may cause immunomodulatory effects comparable to MSC without additional side effects. We used MSC-derived EV in a rat renal transplant model for acute rejection. We analysed peripheral blood leukocytes (PBL), kidney function, graft infiltrating cells, cytokines in the graft, and alloantibody development in animals without (allo) and with EV application (allo EV). There was no difference in kidney function and in the PBL subpopulation including Tregs between allo and allo EV. In the grafts T- and B-cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo. TNF-α transcription was lower in allo EV grafts compared to allo; there was no difference regarding IL-10 and in the development of alloantibodies. In conclusion, the different cell infiltrates and cytokine transcription suggest distinct immunomodulatory properties of EV in allotransplantation. While the increased T- and B-cells in the allo EV grafts may represent a miss...Continue Reading

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Citations

Jul 28, 2016·Nefrología : publicación oficial de la Sociedad Española Nefrologia·Jordi RoviraMaría José Ramírez-Bajo
Jul 8, 2017·International Journal of Molecular Sciences·Verena BörgerBernd Giebel
Mar 18, 2020·Frontiers in Immunology·Marco QuagliaVincenzo Cantaluppi
Sep 1, 2017·American Journal of Physiology. Renal Physiology·Eva FeigerlováJean-Louis Guéant
Dec 12, 2018·Journal of Cellular Physiology·Kaveh BaghaeiSeyed Mahmoud Hashemi
Nov 24, 2020·Hypertension·Olga Martinez-ArroyoRaquel Cortes
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Riccardo BazzoniMauro Krampera
Apr 2, 2021·Stem Cell Research & Therapy·Yuling Huang, Lina Yang
Apr 16, 2021·Bio-protocol·María José Ramírez-BajoFritz Diekmann

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Methods Mentioned

BETA
flow cytometry
FCS
PCR

Software Mentioned

GraphPad
FlowJo
GraphPad Prism

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