Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts.

Proceedings of the National Academy of Sciences of the United States of America
Rutger-Jan SwijnenburgJoseph C Wu

Abstract

Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not well characterized. In fact, controversy remains as to whether hESCs have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging to track the fate of transplanted hESCs stably transduced with a double-fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show that survival after transplant is significantly limited in immunocompetent as opposed to immunodeficient mice. Repeated transplantation of hESCs into immunocompetent hosts results in accelerated hESC death, suggesting an adaptive donor-specific immune response. Our data demonstrate that transplanted hESCs trigger robust cellular and humoral immune responses, resulting in intragraft infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we have found CD4(+) T cells to be an important modulator of hESC immune-mediated rejection. Finally, we show that immunosuppressive drug regimens can mitigate the anti-hESC immune response and that a regimen of combined tacrolimus and sir...Continue Reading

References

May 23, 1998·Annual Review of Immunology·H Auchincloss, D H Sachs
Nov 6, 1998·Science·J A ThomsonJ M Jones
Dec 28, 1999·Transplantation·T UchidaH Yasui
May 30, 2002·Journal of Anatomy·Jonathan S DraperPeter W Andrews
Jul 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Micha DrukkerNissim Benvenisty
Sep 10, 2002·Transplant Immunology·David S Game, Robert I Lechler
Nov 5, 2002·Nature Reviews. Immunology·J Andrew BradleyRoger A Pedersen
Feb 13, 2003·The Journal of Thoracic and Cardiovascular Surgery·Jiang-Yong MinYong-Fu Xiao
Apr 30, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Abhijit DeSanjiv Sam Gambhir
Dec 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yu-An CaoChristopher H Contag
Jul 28, 2004·Stem Cells·Li LiMickie Bhatia
Nov 19, 2004·Springer Seminars in Immunopathology·Micha Drukker
Jul 26, 2005·Critical Reviews in Oncology/hematology·Anna L TaylorJ Andrew Bradley
Dec 16, 2006·Reproductive Biomedicine Online·Karl-Henrik GrinnemoGöran Dellgren
Sep 12, 2007·Cell and Tissue Research·Karl-Henrik GrinnemoMatthias Corbascio
Oct 27, 2007·Stem Cells·Cody A KochJeffrey L Platt
Nov 6, 2007·Journal of the American College of Cardiology·Oren CaspiLior Gepstein
Dec 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nathan J RobertsonPaul J Fairchild

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Citations

Feb 17, 2009·Biogerontology·Jan O Nehlin, Torben Barington
Jun 19, 2012·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Yang LiFan Wang
Jun 1, 2012·International Journal of Hematology·Yasuhiro EbiharaKohichiro Tsuji
Jun 19, 2010·Journal of Cardiovascular Translational Research·Ma Eugenia Vázquez-AlvarezFrancisco Fernández-Avilés
May 4, 2011·Journal of Cardiovascular Translational Research·Wendy Y ZhangJoseph C Wu
Mar 14, 2012·Journal of Cardiovascular Translational Research·Philippe Menasché
May 14, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marcel M DaadiGary K Steinberg
Mar 12, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Philippe Menasche
Jun 2, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kazim H Narsinh, Joseph C Wu
Jul 10, 2009·Nature Biotechnology·Melissa K CarpenterMahendra S Rao
May 5, 2011·Nature Cell Biology·Sean M Wu, Konrad Hochedlinger
Aug 8, 2013·Nature Medicine·Andrew S LeeJoseph C Wu
Jul 21, 2009·Nature Protocols·Ning SunJoseph C Wu
Nov 26, 2010·Nature Reviews. Immunology·Paul J Fairchild
Apr 3, 2012·Biologie aujourd'hui·Philippe Menasché
May 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Giuseppe Maria de PeppoDarja Marolt
Oct 2, 2012·The Journal of Biological Chemistry·Ling ZhangTing C Zhao
Mar 17, 2009·Stem Cells and Development·Kitchener D WilsonJoseph C Wu
May 9, 2012·Stem Cells and Development·Anna ZimmermannJean Villard
Oct 27, 2009·Current Opinion in Organ Transplantation·Christopher N Mayhew, James M Wells
Feb 24, 2012·Current Opinion in Neurology·Yong Wook JungIn-Hyun Park
Nov 21, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Huan-Ting LinHiromitsu Nakauchi
Dec 18, 2012·Science Translational Medicine·Jeremy I PearlJoseph C Wu
Jun 15, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Patricia E de AlmeidaJoseph C Wu
Apr 30, 2011·Circulation Research·Kamileh NarsinhJoseph C Wu
Oct 1, 2011·Circulation Research·Patricia K NguyenJoseph C Wu
Feb 2, 2013·Circulation Research·Patricia E de AlmeidaJoseph C Wu
Sep 30, 2009·Circulation·Katja Schenke-Layland, W Robb MacLellan
Feb 2, 2011·Circulation·Ian Y Chen, Joseph C Wu
Oct 8, 2011·Cell & Bioscience·Junke ZhengCheng Cheng Zhang
Mar 26, 2009·Regenerative Medicine·Ornella ParoliniDörthe Schmidt
Apr 17, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Joseph C WuDara L Kraitchman
May 25, 2011·World Journal of Stem Cells·Francesco BifariMauro Krampera
Feb 26, 2014·Stem Cells and Development·Morteza JalaliLudovic Vallier
Jan 21, 2014·Experimental Hematology·Heather L ThompsonJennifer O Manilay

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