Hypoxia Inducible Factor-1α Potentiates Jagged 1-Mediated Angiogenesis by Mesenchymal Stem Cell-Derived Exosomes.
Hernán González-King,Nahuel A. García,Imelda Ontoria-Oviedo,María Ciria,José Anastasio Montero,Pilar Sepúlveda +5 more
Reads0
Chats0
TLDR
Exosomes derived from MSCs stably overexpressing HIF‐1α have an increased angiogenic capacity in part via an increase in the packaging of Jagged1, which could have potential applications for the treatment of ischemia‐related disease.Abstract:
Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here, we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC. Omics analysis of miRNAs and proteins incorporated into exosomes pointed to the Notch pathway as a candidate mediator of exosome communication. Interestingly, we found that Jagged1 was the sole Notch ligand packaged into MSC exosomes and was more abundant in HIF-MSC than in MSC controls. The addition of Jagged1-containing exosomes from MSC and HIF-MSC cultures to endothelial cells triggered transcriptional changes in Notch target genes and induced angiogenesis in an in vitro model of capillary-like tube formation, and both processes were stimulated by HIF-1α. Finally, subcutaneous injection of Jagged 1-containing exosomes from MSC and HIF-MSC cultures in the Matrigel plug assay induced angiogenesis in vivo, which was more robust when they were derived from HIF-MSC cultures. All Jagged1-mediated effects could be blocked by prior incubation of exosomes with an anti-Jagged 1 antibody. All together, the results indicate that exosomes derived from MSCs stably overexpressing HIF-1α have an increased angiogenic capacity in part via an increase in the packaging of Jagged1, which could have potential applications for the treatment of ischemia-related disease. Stem Cells 2017;35:1747-1759.read more
Citations
More filters
Journal ArticleDOI
Stem Cell Extracellular Vesicles in Skin Repair
TL;DR: This review focuses on recent studies that explore the potential of stem cell EVs in skin wound healing and skin rejuvenation, as well as challenges of their use in therapy.
Journal ArticleDOI
Extracellular vesicles for tissue repair and regeneration: evidence, challenges and opportunities
Anika Nagelkerke,Miina Ojansivu,Luke van der Koog,Luke van der Koog,Thomas E. Whittaker,Eoghan M. Cunnane,Andreia M. Silva,Niek Dekker,Molly M. Stevens +8 more
TL;DR: Extracellular vesicles (EVs) are biological nanoparticles naturally secreted by cells, acting as delivery vehicles for molecular messages as discussed by the authors, and have been assigned multiple functions that have established their potential as therapeutic mediators for a variety of diseases and conditions.
Journal ArticleDOI
Small extracellular vesicles obtained from hypoxic mesenchymal stromal cells have unique characteristics that promote cerebral angiogenesis, brain remodeling and neurological recovery after focal cerebral ischemia in mice.
Jonas Gregorius,Chen Wang,Oumaima Stambouli,Tanja Hussner,Yachao Qi,Tobias Tertel,Verena Börger,Ayan Mohamud Yusuf,Nina Hagemann,Dongpei Yin,Robin Dittrich,Yanis Mouloud,Fabian Dominik Mairinger,Fouzi El Magraoui,Aurel Popa-Wagner,Christoph Kleinschnitz,Thorsten R. Doeppner,Matthias Gunzer,Matthias Gunzer,Helmut E. Meyer,Helmut E. Meyer,Bernd Giebel,Dirk M. Hermann +22 more
TL;DR: In this paper, mesenchymal stromal cells (MSC)-derived small extracellular vesicles (sEVs) were evaluated on the proliferation, migration, and tube formation of human cerebral microvascular endothelial cells (hCMEC/D3) in vitro and on post-ischemic angiogenesis, brain remodeling and neurological recovery after middle cerebral artery occlusion (MCAO) in mice.
Journal ArticleDOI
An Analysis of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Preclinical Use.
Alvin Tieu,Manoj M. Lalu,Mitchell Slobodian,Catherine Gnyra,Dean Fergusson,Joshua Montroy,Dylan Burger,Duncan J. Stewart,David S. Allan +8 more
TL;DR: Knowledge gaps identified from this systematic review highlight important opportunities to improve preclinical design and methodology in the rapidly growing field of EV therapeutics.
Journal ArticleDOI
Cell-Based Therapy in Cardiac Regeneration: An Overview.
TL;DR: A comprehensive review of the use of cell therapy for cardiac regeneration can be found in the Compendium by Banarjee, Bolli, and Hare as mentioned in this paper, where important observations have led to more questions and challenges.
References
More filters
Journal ArticleDOI
Notch Signaling: Cell Fate Control and Signal Integration in Development
TL;DR: Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development, providing a general developmental tool to influence organ formation and morphogenesis.
Journal ArticleDOI
Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
TL;DR: This unit describes different approaches for exosome purification from various sources, and discusses methods to evaluate the purity and homogeneity of the purified exosomes preparations.
Journal ArticleDOI
Membrane vesicles as conveyors of immune responses
TL;DR: The role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells is focused on.
Journal ArticleDOI
Tumour exosome integrins determine organotropic metastasis
Ayuko Hoshino,Bruno Costa-Silva,Tang-Long Shen,Gonçalo Rodrigues,Ayako Hashimoto,Milica Tesic Mark,Henrik Molina,Shinji Kohsaka,Angela Di Giannatale,Sophia Ceder,Swarnima Singh,Caitlin Williams,Nadine Soplop,Kunihiro Uryu,Lindsay A. Pharmer,Tari A. King,Linda Bojmar,Alexander E. Davies,Yonathan Ararso,Tuo Zhang,Haiying Zhang,Jonathan M. Hernandez,Joshua Mitchell Weiss,Vanessa D. Dumont-Cole,Kimberly Kramer,Leonard H. Wexler,Aru Narendran,Gary K. Schwartz,John H. Healey,Per Sandström,Knut Jørgen Labori,Elin H. Kure,Paul M. Grandgenett,Michael A. Hollingsworth,Maria de Sousa,Sukwinder Kaur,Maneesh Jain,Kavita Mallya,Surinder K. Batra,William R. Jarnagin,Mary S. Brady,Øystein Fodstad,Volkmar Müller,Klaus Pantel,Andy J. Minn,Mina J. Bissell,Benjamin A. Garcia,Yibin Kang,Yibin Kang,Vinagolu K. Rajasekhar,Cyrus M. Ghajar,Irina Matei,Héctor Peinado,Jacqueline Bromberg,Jacqueline Bromberg,David Lyden +55 more
TL;DR: It is demonstrated that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells.
Journal ArticleDOI
Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views.
TL;DR: Critically evaluate the literature describing the plasticity of MSCs and offer insight into how the molecular and functional heterogeneity of this cell population, which reflects the complexity of marrow stroma as an organ system, may confound interpretation of their transdifferentiation potential.
Related Papers (5)
Minimal information for studies of extracellular vesicles 2018 (MISEV2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
Clotilde Théry,Kenneth W. Witwer,Elena Aikawa,María José Alcaraz,Johnathon D. Anderson,Ramaroson Andriantsitohaina,Anna Antoniou,Anna Antoniou,Tanina Arab,Fabienne Archer,Georgia K. Atkin-Smith,D. Craig Ayre,Jean Marie Bach,Daniel Bachurski,Hossein Baharvand,Hossein Baharvand,Leonora Balaj,Shawn Baldacchino,Natalie N. Bauer,Amy A. Baxter,Mary Bebawy,Carla Beckham,Apolonija Bedina Zavec,Abderrahim Benmoussa,Anna Berardi,Paolo Bergese,Ewa Bielska,Cherie Blenkiron,Sylwia Bobis-Wozowicz,Eric Boilard,Wilfrid Boireau,Antonella Bongiovanni,Francesc E. Borràs,Steffi Bosch,Chantal M. Boulanger,Chantal M. Boulanger,Xandra O. Breakefield,Andrew M. Breglio,Andrew M. Breglio,Meadhbh Á. Brennan,Meadhbh Á. Brennan,David R. Brigstock,David R. Brigstock,Alain Brisson,Marike L. D. Broekman,Marike L. D. Broekman,Jacqueline Bromberg,Paulina Bryl-Górecka,Shilpa Buch,Amy H. Buck,Dylan Burger,Sara Busatto,Sara Busatto,Dominik Buschmann,Benedetta Bussolati,Edit I. Buzás,Edit I. Buzás,James Bryan Byrd,Giovanni Camussi,David R. F. Carter,Sarah Caruso,Lawrence W. Chamley,Yu Ting Chang,Amrita Datta Chaudhuri,Chihchen Chen,Shuai Chen,Lesley Cheng,Andrew Chin,Aled Clayton,Stefano P. Clerici,Alex Cocks,Emanuele Cocucci,Robert J. Coffey,Anabela Cordeiro-da-Silva,Yvonne Couch,Frank A. W. Coumans,Beth Coyle,Rossella Crescitelli,Miria Ferreira Criado,Crislyn D'Souza-Schorey,Saumya Das,Paola de Candia,Eliezer F. De Santana,Olivier De Wever,Hernando A. del Portillo,Tanguy Demaret,Sarah Deville,Sarah Deville,Andrew Devitt,Bert Dhondt,Dolores Di Vizio,Lothar C. Dieterich,Vincenza Dolo,Ana Paula Domínguez Rubio,Massimo Dominici,Mauricio Rocha Dourado,Mauricio Rocha Dourado,Tom A. P. Driedonks,Filipe V. Duarte,Heather M. Duncan,Ramon M. Eichenberger,Karin M. Ekström,Samir El Andaloussi,Celine Elie-Caille,Uta Erdbrügger,Juan M. Falcón-Pérez,Farah Fatima,Jason E. Fish,Jason E. Fish,Miguel Flores-Bellver,András Försönits,Annie Frelet-Barrand,Fabia Fricke,Fabia Fricke,Gregor Fuhrmann,Susanne Gabrielsson,Ana Gámez-Valero,Chris Gardiner,Kathrin Gärtner,Raphael Gaudin,Raphael Gaudin,Yong Song Gho,Bernd Giebel,Caroline Gilbert,Mario Gimona,Ilaria Giusti,Deborah C.I. Goberdhan,André Görgens,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 Holthöfer,Baharak Hosseinkhani,Guoku Hu,Yiyao Huang,Yiyao Huang,Veronica Huber,Stuart Hunt,Ahmed Ibrahim,Tsuneya Ikezu,Jameel M. Inal,Mustafa Isin,Alena Ivanova,Hannah K Jackson,Søren Jacobsen,Steven M. Jay,Muthuvel Jayachandran,Guido Jenster,Lanzhou Jiang,Suzanne M. Johnson,Jennifer Jones,Ambrose Jong,Tijana Jovanovic-Talisman,Stephanie M. Jung,Raghu Kalluri,Shin Ichi Kano,Sukhbir Kaur,Yumi Kawamura,Yumi Kawamura,Evan T. Keller,Delaram Khamari,Elena Khomyakova,Anastasia Khvorova,Peter Kierulf,Kwang Pyo Kim,Thomas Kislinger,Thomas Kislinger,Mikael Klingeborn,David J. Klinke,Miroslaw Kornek,Maja Kosanović,Árpád Kovács,Eva-Maria Krämer-Albers,Susanne Krasemann,Mirja Krause,Igor V. Kurochkin,Gina D. Kusuma,Gina D. Kusuma,Sören Kuypers,Saara Laitinen,Scott M. Langevin,Lucia R. Languino,Joanne Lannigan,Cecilia Lässer,Louise C. Laurent,Grégory Lavieu,Elisa Lázaro-Ibáñez,Soazig Le Lay,Myung-Shin Lee,Yi Xin Fiona Lee,Débora S. Lemos,Metka Lenassi,Aleksandra Leszczynska,Isaac T. S. Li,Ke Liao,Sten F.W.M. Libregts,Erzsébet Ligeti,Rebecca Lim,Rebecca Lim,Sai Kiang Lim,Aija Linē,Karen Linnemannstöns,Alicia Llorente,Catherine Lombard,Magdalena J. Lorenowicz,Ákos M. Lörincz,Jan Lötvall,Jason Lovett,Michelle C. Lowry,Xavier Loyer,Xavier Loyer,Quan Lu,Barbara Lukomska,Taral R. Lunavat,Sybren L. N. Maas,Harmeet Malhi,Antonio Marcilla,Jacopo Mariani,Javier Mariscal,Elena S. Martens-Uzunova,Lorena Martin-Jaular,M. Carmen Martinez,Vilma R. Martins,Mathilde Mathieu,Suresh Mathivanan,Marco Maugeri,Lynda K. McGinnis,Mark J. McVey,David G. Meckes,Katie Meehan,Inge Mertens,Inge Mertens,Valentina R. Minciacchi,Andreas Möller,Malene Jørgensen,Aizea Morales-Kastresana,Jess Morhayim,François Mullier,Maurizio Muraca,Luca Musante,Veronika Mussack,Dillon C. Muth,Kathryn H. Myburgh,Tanbir Najrana,Muhammad Nawaz,Irina Nazarenko,Irina Nazarenko,Peter Nejsum,Christian Neri,Tommaso Neri,Rienk Nieuwland,Leonardo Nimrichter,John P. Nolan,Esther N. M. Nolte-‘t Hoen,Nicole Noren Hooten,Lorraine O'Driscoll,Tina O'Grady,Ana O'Loghlen,Takahiro Ochiya,Martin Olivier,Alberto Ortiz,Luis A. Ortiz,Xabier Osteikoetxea,Ole Ostegaard,Ole Ostegaard,Matias Ostrowski,Jaesung Park,D. Michiel Pegtel,Héctor Peinado,Francesca Perut,Michael W. Pfaffl,Donald G. Phinney,Bartijn C. H. Pieters,Ryan C. Pink,David S. Pisetsky,Elke Pogge von Strandmann,Iva Polakovicova,Ivan K. H. Poon,Bonita H. Powell,Ilaria Prada,Lynn Pulliam,Lynn Pulliam,Peter J. Quesenberry,Annalisa Radeghieri,Robert L. Raffai,Robert L. Raffai,Stefania Raimondo,Janusz Rak,Marcel I. Ramirez,Marcel I. Ramirez,Graça Raposo,Morsi S. Rayyan,Neta Regev-Rudzki,Franz Ricklefs,Paul D. Robbins,David D. Roberts,Silvia C Rodrigues,Eva Rohde,Sophie Rome,Kasper M.A. Rouschop,Aurelia Rughetti,Ashley E. Russell,Paula Saa,Susmita Sahoo,Edison Salas-Huenuleo,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 Siljander,Andreia M. Silva,Agata Skowronek,Orman L. Snyder,Rodrigo Pedro Soares,Barbara W Sódar,Carolina Soekmadji,Carolina Soekmadji,Javier Sotillo,Philip D. Stahl,Willem Stoorvogel,Shannon L. Stott,Erwin Strasser,Simon Swift,Hidetoshi Tahara,Muneesh Tewari,Kate Timms,Swasti Tiwari,Swasti Tiwari,Rochelle Tixeira,Mercedes Tkach,Wei Seong Toh,Richard Tomasini,Ana Claudia Torrecilhas,Juan Pablo Tosar,Juan Pablo Tosar,Vasilis Toxavidis,Lorena Urbanelli,Pieter Vader,Bas W.M. van Balkom,Susanne G. van der Grein,Jan Van Deun,Martijn J. C. van Herwijnen,Kendall Van Keuren-Jensen,Guillaume van Niel,Martin E. van Royen,Andre J. van Wijnen,M. Helena Vasconcelos,Ivan J. Vechetti,Tiago Degani Veit,Laura J Vella,Laura J Vella,Emilie Velot,Frederik J. Verweij,Beate Vestad,Jose L. Viñas,Tamás Visnovitz,Krisztina V. Vukman,Jessica Wahlgren,Dionysios C. Watson,Marca H. M. Wauben,Alissa M. Weaver,Jason P. Webber,Viktoria Weber,Ann M. Wehman,Daniel J. Weiss,Joshua A. Welsh,Sebastian Wendt,Åsa M. Wheelock,Zoltán Wiener,Leonie Witte,Joy Wolfram,Joy Wolfram,Joy Wolfram,Angeliki Xagorari,Patricia Xander,Jing Xu,Xiaomei Yan,María Yáñez-Mó,María Yáñez-Mó,Hang Yin,Yuana Yuana,Valentina Zappulli,Jana Zarubova,Jana Zarubova,Vytautas Žėkas,Jian ye Zhang,Zezhou Zhao,Lei Zheng,Alexander R. Zheutlin,Antje M. Zickler,Pascale Zimmermann,Pascale Zimmermann,Angela M. Zivkovic,Davide Zocco,Ewa K. Zuba-Surma +417 more