Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections.

Autor: Ackermann M; JRG Translational Hematology of Congenital Diseases, Hannover Medical School, Hannover, Germany.; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany., Kempf H; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany.; Department of Stem Cell Biology, Novo Nordisk A/S, 2760, Maaloev, Denmark., Hetzel M; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany.; RG Reprogramming and Gene Therapy, Hannover Medical School, 30625, Hannover, Germany., Hesse C; Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), REBIRTH Cluster-of Excellence, 30625, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany., Hashtchin AR; JRG Translational Hematology of Congenital Diseases, Hannover Medical School, Hannover, Germany.; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany., Brinkert K; Clinical Research Group 'Cystic Fibrosis', Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625, Hannover, Germany., Schott JW; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany., Haake K; JRG Translational Hematology of Congenital Diseases, Hannover Medical School, Hannover, Germany.; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany., Kühnel MP; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany.; Institute for Pathology, Hannover Medical School, 30625, Hannover, Germany., Glage S; Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany., Figueiredo C; Institute for Transfusion Medicine, Hannover Medical School, 30625, Hannover, Germany., Jonigk D; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany.; Institute for Pathology, Hannover Medical School, 30625, Hannover, Germany., Sewald K; Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), REBIRTH Cluster-of Excellence, 30625, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany., Schambach A; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02215, USA., Wronski S; Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), REBIRTH Cluster-of Excellence, 30625, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany., Moritz T; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany.; RG Reprogramming and Gene Therapy, Hannover Medical School, 30625, Hannover, Germany., Martin U; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany., Zweigerdt R; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany., Munder A; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625, Hannover, Germany.; Clinical Research Group 'Cystic Fibrosis', Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625, Hannover, Germany., Lachmann N; JRG Translational Hematology of Congenital Diseases, Hannover Medical School, Hannover, Germany. lachmann.nico@mh-hannover.de.; Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical School, 30625, Hannover, Germany. lachmann.nico@mh-hannover.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Nov 30; Vol. 9 (1), pp. 5088. Date of Electronic Publication: 2018 Nov 30.
DOI: 10.1038/s41467-018-07570-7
Abstrakt: The increasing number of severe infections with multi-drug-resistant pathogens worldwide highlights the need for alternative treatment options. Given the pivotal role of phagocytes and especially alveolar macrophages in pulmonary immunity, we introduce a new, cell-based treatment strategy to target bacterial airway infections. Here we show that the mass production of therapeutic phagocytes from induced pluripotent stem cells (iPSC) in industry-compatible, stirred-tank bioreactors is feasible. Bioreactor-derived iPSC-macrophages (iPSC-Mac) represent a highly pure population of CD45 + CD11b + CD14 + CD163 + cells, and share important phenotypic, functional and transcriptional hallmarks with professional phagocytes, however with a distinct transcriptome signature similar to primitive macrophages. Most importantly, bioreactor-derived iPSC-Mac rescue mice from Pseudomonas aeruginosa-mediated acute infections of the lower respiratory tract within 4-8 h post intra-pulmonary transplantation and reduce bacterial load. Generation of specific immune-cells from iPSC-sources in scalable stirred-tank bioreactors can extend the field of immunotherapy towards bacterial infections, and may allow for further innovative cell-based treatment strategies.
Databáze: MEDLINE
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