James A Hutchinson1, Paloma Riquelme, Edward K Geissler. 1. Department of Surgery, Laboratory for Transplantation Research, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Germany. james.hutchinson@klinik.uni-regensburg.de
Abstract
PURPOSE OF REVIEW: To consolidate our basic scientific and technological appreciation of human regulatory macrophages (M reg) as a cell-based medicinal product for use as an adjunct immunosuppressive therapy in organ transplantation. RECENT FINDINGS: Building on the original observation that crude preparations of IFN-γ-stimulated allogeneic macrophages prolong allograft survival in experimental animals, we have arrived at a detailed understanding of the derivation, phenotype and T-cell-suppressive potential of a population of in-vitro-derived human macrophages, which have been designated M regs. This basic scientific knowledge has inspired methodological advances in M reg manufacture, leading to a purer and more homogeneous cell product. In turn, cells produced by these improved protocols have been applied in the clinic, so completing a cycle of technological development. Studying the migration and physiological impact of M reg administration in patients provides a measure of reassurance that the procedure is well tolerated. Cutting-edge strategies to assess the immunological status of solid organ transplant recipients allow the biological effects of M reg treatment to be monitored. SUMMARY: A view of the human M reg as a novel, stringently defined medicinal product is presented, opening exciting possibilities for its future investigation as a therapy in solid organ transplantation and beyond.
PURPOSE OF REVIEW: To consolidate our basic scientific and technological appreciation of human regulatory macrophages (M reg) as a cell-based medicinal product for use as an adjunct immunosuppressive therapy in organ transplantation. RECENT FINDINGS: Building on the original observation that crude preparations of IFN-γ-stimulated allogeneic macrophages prolong allograft survival in experimental animals, we have arrived at a detailed understanding of the derivation, phenotype and T-cell-suppressive potential of a population of in-vitro-derived human macrophages, which have been designated M regs. This basic scientific knowledge has inspired methodological advances in M reg manufacture, leading to a purer and more homogeneous cell product. In turn, cells produced by these improved protocols have been applied in the clinic, so completing a cycle of technological development. Studying the migration and physiological impact of M reg administration in patients provides a measure of reassurance that the procedure is well tolerated. Cutting-edge strategies to assess the immunological status of solid organ transplant recipients allow the biological effects of M reg treatment to be monitored. SUMMARY: A view of the human M reg as a novel, stringently defined medicinal product is presented, opening exciting possibilities for its future investigation as a therapy in solid organ transplantation and beyond.
Authors: Paloma Riquelme; Stefan Tomiuk; Anja Kammler; Fred Fändrich; Hans J Schlitt; Edward K Geissler; James A Hutchinson Journal: Mol Ther Date: 2012-08-28 Impact factor: 11.454
Authors: Christiane Broichhausen; Paloma Riquelme; Norbert Ahrens; Anja K Wege; Gudrun E Koehl; Hans J Schlitt; Bernhard Banas; Fred Fändrich; Edward K Geissler; James A Hutchinson Journal: Mol Ther Methods Clin Dev Date: 2014-07-16 Impact factor: 6.698
Authors: Phillip Lord; Catharien M U Hilkens; Rachel Spiering; Juan C Aguillon; Amy E Anderson; Silke Appel; Daniel Benitez-Ribas; Anja Ten Brinke; Femke Broere; Nathalie Cools; Maria Cristina Cuturi; Julie Diboll; Edward K Geissler; Nick Giannoukakis; Silvia Gregori; S Marieke van Ham; Staci Lattimer; Lindsay Marshall; Rachel A Harry; James A Hutchinson; John D Isaacs; Irma Joosten; Cees van Kooten; Ascension Lopez Diaz de Cerio; Tatjana Nikolic; Haluk Barbaros Oral; Ljiljana Sofronic-Milosavljevic; Thomas Ritter; Paloma Riquelme; Angus W Thomson; Massimo Trucco; Marta Vives-Pi; Eva M Martinez-Caceres Journal: PeerJ Date: 2016-08-30 Impact factor: 2.984
Authors: Ondrej Viklicky; Petra Hruba; Stefan Tomiuk; Sabrina Schmitz; Bernhard Gerstmayer; Birgit Sawitzki; Patrick Miqueu; Petra Mrazova; Irena Tycova; Eva Svobodova; Eva Honsova; Uwe Janssen; Hans-Dieter Volk; Petra Reinke Journal: PLoS One Date: 2017-01-13 Impact factor: 3.240
Authors: Mathias Streitz; Tewfik Miloud; Michael Kapinsky; Michael R Reed; Robert Magari; Edward K Geissler; James A Hutchinson; Katrin Vogt; Stephan Schlickeiser; Anders Handrup Kverneland; Christian Meisel; Hans-Dieter Volk; Birgit Sawitzki Journal: Transplant Res Date: 2013-10-25