H Dihazi1, K Schwarze1, S Patschan2, G A Müller1, O Ritter2, M Zeisberg1, D Patschan2. 1. Klinik für Nephrologie und Rheumatologie, Universitätsmedizin Göttingen, Göttingen, Germany. 2. Zentrum für Innere Medizin 1, Klinikum Brandenburg, Medizinische Hochschule Brandenburg, Brandenburg, Germany.
Abstract
INTRODUCTION: Acute kidney injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as a reliable option for improving AKI outcomes in experimental AKI. Our previous studies focused on the so-called proangiogenic cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production/secretion of extracellular vesicles (MV, microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and/or the secretome alone. METHODS: AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI-40 minutes). Syngeneic murine PACs were stimulated with either melatonin, angiopoietin-1 or -2, or with bone morphogenetic protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v.-injected after ischemia. Mice were analyzed 48 hours later. RESULTS: IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened after ischemic renal function even further: MV + Ang-1, MV + BMP-5, MV + melatonin, and MV + secretome + Ang-1. CONCLUSION: Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonin, BMP-5), mechanisms other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.
INTRODUCTION: Acute kidney injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as a reliable option for improving AKI outcomes in experimental AKI. Our previous studies focused on the so-called proangiogenic cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production/secretion of extracellular vesicles (MV, microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and/or the secretome alone. METHODS: AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI-40 minutes). Syngeneic murine PACs were stimulated with either melatonin, angiopoietin-1 or -2, or with bone morphogenetic protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v.-injected after ischemia. Mice were analyzed 48 hours later. RESULTS: IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened after ischemic renal function even further: MV + Ang-1, MV + BMP-5, MV + melatonin, and MV + secretome + Ang-1. CONCLUSION: Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonin, BMP-5), mechanisms other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.
Authors: Junying Yu; Maxim A Vodyanik; Kim Smuga-Otto; Jessica Antosiewicz-Bourget; Jennifer L Frane; Shulan Tian; Jeff Nie; Gudrun A Jonsdottir; Victor Ruotti; Ron Stewart; Igor I Slukvin; James A Thomson Journal: Science Date: 2007-11-20 Impact factor: 47.728
Authors: Daniel Patschan; Krystina Krupincza; Susann Patschan; Zhongtao Zhang; Carl Hamby; Michael S Goligorsky Journal: Am J Physiol Renal Physiol Date: 2006-02-14
Authors: Andrea Ranghino; Stefania Bruno; Benedetta Bussolati; Aldo Moggio; Veronica Dimuccio; Marta Tapparo; Luigi Biancone; Paolo Gontero; Bruno Frea; Giovanni Camussi Journal: Stem Cell Res Ther Date: 2017-02-07 Impact factor: 6.832
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Andrew R Chin; Aled Clayton; Stefano P Clerici; Alex Cocks; Emanuele Cocucci; Robert J Coffey; Anabela Cordeiro-da-Silva; Yvonne Couch; Frank Aw Coumans; Beth Coyle; Rossella Crescitelli; Miria Ferreira Criado; Crislyn D'Souza-Schorey; Saumya Das; Amrita Datta Chaudhuri; Paola de Candia; Eliezer F De Santana; Olivier De Wever; Hernando A Del Portillo; Tanguy Demaret; Sarah Deville; Andrew Devitt; Bert Dhondt; Dolores Di Vizio; Lothar C Dieterich; Vincenza Dolo; Ana Paula Dominguez Rubio; Massimo Dominici; Mauricio R Dourado; Tom Ap Driedonks; Filipe V Duarte; Heather M Duncan; Ramon M Eichenberger; Karin Ekström; Samir El Andaloussi; Celine Elie-Caille; Uta Erdbrügger; Juan M Falcón-Pérez; Farah Fatima; Jason E Fish; Miguel Flores-Bellver; András Försönits; Annie Frelet-Barrand; Fabia Fricke; Gregor Fuhrmann; Susanne Gabrielsson; Ana Gámez-Valero; Chris Gardiner; Kathrin Gärtner; Raphael Gaudin; Yong Song Gho; Bernd Giebel; Caroline Gilbert; Mario Gimona; Ilaria Giusti; Deborah Ci Goberdhan; André Görgens; Sharon M Gorski; David W Greening; Julia Christina Gross; Alice Gualerzi; Gopal N Gupta; Dakota Gustafson; Aase Handberg; Reka A Haraszti; Paul Harrison; Hargita Hegyesi; An Hendrix; Andrew F Hill; Fred H Hochberg; Karl F Hoffmann; Beth Holder; Harry Holthofer; Baharak Hosseinkhani; Guoku Hu; Yiyao Huang; Veronica Huber; Stuart Hunt; Ahmed Gamal-Eldin Ibrahim; Tsuneya Ikezu; Jameel M Inal; Mustafa Isin; Alena Ivanova; Hannah K Jackson; Soren Jacobsen; Steven M Jay; Muthuvel Jayachandran; Guido Jenster; Lanzhou Jiang; Suzanne M Johnson; Jennifer C Jones; Ambrose Jong; Tijana Jovanovic-Talisman; Stephanie Jung; Raghu Kalluri; Shin-Ichi Kano; Sukhbir Kaur; Yumi Kawamura; Evan T Keller; Delaram Khamari; Elena Khomyakova; Anastasia Khvorova; Peter Kierulf; Kwang Pyo Kim; Thomas Kislinger; Mikael Klingeborn; David J Klinke; Miroslaw Kornek; Maja M Kosanović; Árpád Ferenc Kovács; Eva-Maria Krämer-Albers; Susanne Krasemann; Mirja Krause; Igor V Kurochkin; Gina D Kusuma; Sören Kuypers; Saara Laitinen; Scott M Langevin; Lucia R Languino; Joanne Lannigan; Cecilia Lässer; Louise C Laurent; Gregory Lavieu; Elisa Lázaro-Ibáñez; Soazig Le Lay; Myung-Shin Lee; Yi Xin Fiona Lee; Debora S Lemos; Metka Lenassi; Aleksandra Leszczynska; Isaac Ts Li; Ke Liao; Sten F Libregts; Erzsebet Ligeti; Rebecca Lim; Sai Kiang Lim; Aija Linē; Karen Linnemannstöns; Alicia Llorente; Catherine A Lombard; Magdalena J Lorenowicz; Ákos M Lörincz; Jan Lötvall; Jason Lovett; Michelle C Lowry; Xavier Loyer; Quan Lu; Barbara Lukomska; Taral R Lunavat; Sybren Ln Maas; Harmeet Malhi; Antonio Marcilla; Jacopo Mariani; Javier Mariscal; Elena S Martens-Uzunova; Lorena Martin-Jaular; M Carmen Martinez; Vilma Regina Martins; Mathilde Mathieu; Suresh Mathivanan; Marco Maugeri; Lynda K McGinnis; Mark J McVey; David G Meckes; Katie L Meehan; Inge Mertens; Valentina R Minciacchi; Andreas Möller; Malene Møller Jørgensen; Aizea Morales-Kastresana; Jess Morhayim; François Mullier; Maurizio Muraca; Luca Musante; Veronika Mussack; 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Catherine Sánchez; Julie A Saugstad; Meike J Saul; Raymond M Schiffelers; Raphael Schneider; Tine Hiorth Schøyen; Aaron Scott; Eriomina Shahaj; Shivani Sharma; Olga Shatnyeva; Faezeh Shekari; Ganesh Vilas Shelke; Ashok K Shetty; Kiyotaka Shiba; Pia R-M Siljander; Andreia M Silva; Agata Skowronek; Orman L Snyder; Rodrigo Pedro Soares; Barbara W Sódar; Carolina Soekmadji; Javier Sotillo; Philip D Stahl; Willem Stoorvogel; Shannon L Stott; Erwin F Strasser; Simon Swift; Hidetoshi Tahara; Muneesh Tewari; Kate Timms; Swasti Tiwari; Rochelle Tixeira; Mercedes Tkach; Wei Seong Toh; Richard Tomasini; Ana Claudia Torrecilhas; Juan Pablo Tosar; Vasilis Toxavidis; Lorena Urbanelli; Pieter Vader; Bas Wm van Balkom; Susanne G van der Grein; Jan Van Deun; Martijn Jc van Herwijnen; Kendall Van Keuren-Jensen; Guillaume van Niel; Martin E van Royen; Andre J van Wijnen; M Helena Vasconcelos; Ivan J Vechetti; Tiago D Veit; Laura J Vella; Émilie Velot; Frederik J Verweij; Beate Vestad; Jose L Viñas; Tamás Visnovitz; 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