Ying Qiu1, Mark M Yun2, Xia Han3, Ruidong Zhao3, Erxia Zhou3, Sheng Yun3. 1. Stem Cell Centre, The First Teaching Hospital, Inner Mongolia Medical University Huhhot, 010050, China ; Department of Clinical Sciences, King's College London SE5 9NU, UK. 2. UCL Medical School, University College London Gower Street, London, WC1E 6BT, UK ; Present address: Heart of England, NHS FT Bordesley Green, East Birmingham, Bq 5ST, UK. 3. Stem Cell Centre, The First Teaching Hospital, Inner Mongolia Medical University Huhhot, 010050, China.
Abstract
BACKGROUND: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. METHODS: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. RESULTS: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. CONCLUSIONS: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft.
BACKGROUND:Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. METHODS: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of humanMHC class II transactivator gene (CIITA) under mouseICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. RESULTS: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. CONCLUSIONS: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft.
Authors: M P De Miguel; S Fuentes-Julián; A Blázquez-Martínez; C Y Pascual; M A Aller; J Arias; F Arnalich-Montiel Journal: Curr Mol Med Date: 2012-06 Impact factor: 2.222
Authors: Viola W Y Leung; Sheng Yun; Marina Botto; Justin C Mason; Talat H Malik; Wenchao Song; Danielle Paixao-Cavalcante; Matthew C Pickering; Joseph J Boyle; Dorian O Haskard Journal: Am J Pathol Date: 2009-09-03 Impact factor: 4.307