Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

doi:10.3402/jev.v4.30087

. 2015 Dec 31:4:30087.

doi: 10.3402/jev.v4.30087. eCollection 2015.

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Thomas Lener ^{1

2}, Mario Gimona ^{1

2}, Ludwig Aigner ¹, Verena Börger ³, Edit Buzas ⁴, Giovanni Camussi ⁵, Nathalie Chaput ^{6

7}, Devasis Chatterjee ^{8

9}, Felipe A Court ¹⁰, Hernando A Del Portillo ^{11

12}, Lorraine O'Driscoll ^{13

14}, Stefano Fais ¹⁵, Juan M Falcon-Perez ^{16

17}, Ursula Felderhoff-Mueser ¹⁸, Lorenzo Fraile ¹⁹, Yong Song Gho ²⁰, André Görgens ³, Ramesh C Gupta ^{21

22}, An Hendrix ²³, Dirk M Hermann ²⁴, Andrew F Hill ²⁵, Fred Hochberg ²⁶, Peter A Horn ³, Dominique de Kleijn ²⁷, Lambros Kordelas ²⁸, Boris W Kramer ²⁹, Eva-Maria Krämer-Albers ³⁰, Sandra Laner-Plamberger ^{1

2}, Saara Laitinen ³¹, Tommaso Leonardi ^{32

33}, Magdalena J Lorenowicz ³⁴, Sai Kiang Lim ³⁵, Jan Lötvall ³⁶, Casey A Maguire ³⁷, Antonio Marcilla ^{38

39}, Irina Nazarenko ⁴⁰, Takahiro Ochiya ⁴¹, Tushar Patel ⁴², Shona Pedersen ⁴³, Gabriella Pocsfalvi ⁴⁴, Stefano Pluchino ³², Peter Quesenberry ^{8

9}, Ilona G Reischl ⁴⁵, Francisco J Rivera ⁴⁶, Ralf Sanzenbacher ⁴⁷, Katharina Schallmoser ^{1

2}, Ineke Slaper-Cortenbach ⁴⁸, Dirk Strunk ⁴⁹, Torsten Tonn ⁵⁰, Pieter Vader ^{51

52}, Bas W M van Balkom ⁵³, Marca Wauben ⁵⁴, Samir El Andaloussi ^{52

55}, Clotilde Théry ^{7

56}, Eva Rohde ^{1

57}, Bernd Giebel ⁵⁸

Affiliations

¹ Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria.
² Department of Blood Group Serology and Transfusion Medicine, University Hospital, Salzburger Landeskliniken GesmbH (SALK), Salzburg, Austria.
³ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁴ Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
⁵ Molecular Biotechnology Center, Department of Medical Sciences, University of Turin, Turin, Italy.
⁶ Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US23 Inserm, Villejuif, France.
⁷ Centre of Clinical Investigation in Biotherapy CICBT 1248, Institut Gustave Roussy, Villejuif, France.
⁸ Division of Hematology & Oncology, Rhode Island Hospital, Providence, RI, USA.
⁹ The Alpert Medical School of Brown University, Providence, RI, USA.
¹⁰ Department of Physiology, Faculty of Biology, Pontificia-Universidad Católica de Chile, Santiago, Chile.
¹¹ ICREA at Barcelona Centre for International Health Research (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
¹² Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain.
¹³ School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland;
¹⁴ Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
¹⁵ Anti-Tumor Drugs Section, Department of Therapeutic Research and Medicines Evaluation, National Institute of Health (ISS), Rome, Italy.
¹⁶ Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain.
¹⁷ IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
¹⁸ Department of Paediatrics I, Neonatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
¹⁹ Departament de Producció Animal, ETSEA, Universitat de Lleida, Lleida, Spain.
²⁰ Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
²¹ Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
²² James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
²³ Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
²⁴ Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²⁵ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
²⁶ Massachusetts General Hospital, Boston, MA, USA.
²⁷ Department of Surgery, YLL School of Medicine, NUS, Singapore, Singapore.
²⁸ Department of Bone Marrow Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²⁹ Experimental Perinatology/Neonatology, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
³⁰ Molecular Cell Biology and Focus Program Translational Neurosciences, University of Mainz, Mainz, Germany.
³¹ Research and Cell Services, Finnish Red Cross Blood Service, Helsinki, Finland.
³² Division of Stem Cell Neurobiology, Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
³³ European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.
³⁴ Department of Cell Biology, Center for Molecular Medicine, University Medical Center, Utrecht, The Netherlands.
³⁵ Institute of Medical Biology, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
³⁶ Krefting Research Centre, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³⁷ Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
³⁸ Dpto. Biología Celular y Parasitologia, Facultat de Farmacia, Universitat de Valencia, Valencia, Spain.
³⁹ Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Universitat de València-Health Research Institute La Fe, Valencia, Spain.
⁴⁰ Institute for Environmental Health Sciences and Hospital Infection Control Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
⁴¹ Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
⁴² Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
⁴³ Centre for Cardiovascular Research, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg University, Aalborg, Denmark.
⁴⁴ Mass Spectrometry and Proteomics, Institute of Biosciences and BioResources, National Research Council of Italy, Naples, Italy.
⁴⁵ BASG - Bundesamt für Sicherheit im Gesundheitswesen - Federal Office for Safety in Health Care, AGES - Agentur für Gesundheit und Ernährungssicherheit - Austrian Agency for Health and Food Safety, Institut Überwachung - Institute Surveillance, Wien, Austria.
⁴⁶ Institute of Molecular Regenerative Medicine, Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria;
⁴⁷ Ralf Sanzenbacher, Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
⁴⁸ Cell Therapy Facility, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴⁹ Experimental & Clinical Cell Therapy Institute, Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
⁵⁰ Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany.
⁵¹ Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵² Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
⁵³ Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵⁴ Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
⁵⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵⁶ INSERM U932, Institut Curie, Paris, France.
⁵⁷ Department of Blood Group Serology and Transfusion Medicine, University Hospital, Salzburger Landeskliniken GesmbH (SALK), Salzburg, Austria; e.rohde@salk.at.
⁵⁸ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; bernd.giebel@uk-essen.de.

PMID: 26725829
PMCID: PMC4698466
DOI: 10.3402/jev.v4.30087

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Thomas Lener et al. J Extracell Vesicles. 2015.

. 2015 Dec 31:4:30087.

doi: 10.3402/jev.v4.30087. eCollection 2015.

Authors

Thomas Lener ^{1

2}, Mario Gimona ^{1

2}, Ludwig Aigner ¹, Verena Börger ³, Edit Buzas ⁴, Giovanni Camussi ⁵, Nathalie Chaput ^{6

7}, Devasis Chatterjee ^{8

9}, Felipe A Court ¹⁰, Hernando A Del Portillo ^{11

12}, Lorraine O'Driscoll ^{13

14}, Stefano Fais ¹⁵, Juan M Falcon-Perez ^{16

17}, Ursula Felderhoff-Mueser ¹⁸, Lorenzo Fraile ¹⁹, Yong Song Gho ²⁰, André Görgens ³, Ramesh C Gupta ^{21

22}, An Hendrix ²³, Dirk M Hermann ²⁴, Andrew F Hill ²⁵, Fred Hochberg ²⁶, Peter A Horn ³, Dominique de Kleijn ²⁷, Lambros Kordelas ²⁸, Boris W Kramer ²⁹, Eva-Maria Krämer-Albers ³⁰, Sandra Laner-Plamberger ^{1

2}, Saara Laitinen ³¹, Tommaso Leonardi ^{32

33}, Magdalena J Lorenowicz ³⁴, Sai Kiang Lim ³⁵, Jan Lötvall ³⁶, Casey A Maguire ³⁷, Antonio Marcilla ^{38

39}, Irina Nazarenko ⁴⁰, Takahiro Ochiya ⁴¹, Tushar Patel ⁴², Shona Pedersen ⁴³, Gabriella Pocsfalvi ⁴⁴, Stefano Pluchino ³², Peter Quesenberry ^{8

9}, Ilona G Reischl ⁴⁵, Francisco J Rivera ⁴⁶, Ralf Sanzenbacher ⁴⁷, Katharina Schallmoser ^{1

2}, Ineke Slaper-Cortenbach ⁴⁸, Dirk Strunk ⁴⁹, Torsten Tonn ⁵⁰, Pieter Vader ^{51

52}, Bas W M van Balkom ⁵³, Marca Wauben ⁵⁴, Samir El Andaloussi ^{52

55}, Clotilde Théry ^{7

56}, Eva Rohde ^{1

57}, Bernd Giebel ⁵⁸

Affiliations

¹ Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria.
² Department of Blood Group Serology and Transfusion Medicine, University Hospital, Salzburger Landeskliniken GesmbH (SALK), Salzburg, Austria.
³ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁴ Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
⁵ Molecular Biotechnology Center, Department of Medical Sciences, University of Turin, Turin, Italy.
⁶ Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US23 Inserm, Villejuif, France.
⁷ Centre of Clinical Investigation in Biotherapy CICBT 1248, Institut Gustave Roussy, Villejuif, France.
⁸ Division of Hematology & Oncology, Rhode Island Hospital, Providence, RI, USA.
⁹ The Alpert Medical School of Brown University, Providence, RI, USA.
¹⁰ Department of Physiology, Faculty of Biology, Pontificia-Universidad Católica de Chile, Santiago, Chile.
¹¹ ICREA at Barcelona Centre for International Health Research (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
¹² Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain.
¹³ School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland;
¹⁴ Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
¹⁵ Anti-Tumor Drugs Section, Department of Therapeutic Research and Medicines Evaluation, National Institute of Health (ISS), Rome, Italy.
¹⁶ Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Spain.
¹⁷ IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
¹⁸ Department of Paediatrics I, Neonatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
¹⁹ Departament de Producció Animal, ETSEA, Universitat de Lleida, Lleida, Spain.
²⁰ Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
²¹ Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
²² James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
²³ Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
²⁴ Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²⁵ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
²⁶ Massachusetts General Hospital, Boston, MA, USA.
²⁷ Department of Surgery, YLL School of Medicine, NUS, Singapore, Singapore.
²⁸ Department of Bone Marrow Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²⁹ Experimental Perinatology/Neonatology, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
³⁰ Molecular Cell Biology and Focus Program Translational Neurosciences, University of Mainz, Mainz, Germany.
³¹ Research and Cell Services, Finnish Red Cross Blood Service, Helsinki, Finland.
³² Division of Stem Cell Neurobiology, Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
³³ European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.
³⁴ Department of Cell Biology, Center for Molecular Medicine, University Medical Center, Utrecht, The Netherlands.
³⁵ Institute of Medical Biology, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
³⁶ Krefting Research Centre, Institute of Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³⁷ Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
³⁸ Dpto. Biología Celular y Parasitologia, Facultat de Farmacia, Universitat de Valencia, Valencia, Spain.
³⁹ Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Universitat de València-Health Research Institute La Fe, Valencia, Spain.
⁴⁰ Institute for Environmental Health Sciences and Hospital Infection Control Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
⁴¹ Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
⁴² Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
⁴³ Centre for Cardiovascular Research, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg University, Aalborg, Denmark.
⁴⁴ Mass Spectrometry and Proteomics, Institute of Biosciences and BioResources, National Research Council of Italy, Naples, Italy.
⁴⁵ BASG - Bundesamt für Sicherheit im Gesundheitswesen - Federal Office for Safety in Health Care, AGES - Agentur für Gesundheit und Ernährungssicherheit - Austrian Agency for Health and Food Safety, Institut Überwachung - Institute Surveillance, Wien, Austria.
⁴⁶ Institute of Molecular Regenerative Medicine, Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria;
⁴⁷ Ralf Sanzenbacher, Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
⁴⁸ Cell Therapy Facility, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴⁹ Experimental & Clinical Cell Therapy Institute, Spinal Cord Injury & Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
⁵⁰ Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany.
⁵¹ Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵² Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
⁵³ Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
⁵⁴ Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
⁵⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵⁶ INSERM U932, Institut Curie, Paris, France.
⁵⁷ Department of Blood Group Serology and Transfusion Medicine, University Hospital, Salzburger Landeskliniken GesmbH (SALK), Salzburg, Austria; e.rohde@salk.at.
⁵⁸ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; bernd.giebel@uk-essen.de.

PMID: 26725829
PMCID: PMC4698466
DOI: 10.3402/jev.v4.30087

Abstract

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Keywords: haematology; immunology; neurobiology; regulation; stem cells; tissue regeneration; tumour vaccination.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Pharmaceutical categories and a suggested classification of EV-based therapeutics. Chart depicts the Categories of Medicinal Products with respect to their origin (chemical, biological, herbal). Medicinal Products (according to DIRECTIVE 2001/83/EC) include any substance or combination of substances for treating or preventing disease in humans. Any substance or combination of substances which may be administered to humans with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans is likewise considered a medicinal product. The suggested classification of EV-based therapeutics within the class of biological medicinal products is provided (grey fields). Bold indicates categories from which existing legislation is recommended to be considered for preclinical and clinical development of EV-therapeutics.

See this image and copyright information in PMC

References

1. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373–83. - PMC - PubMed
1. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4 27066, doi: http://dx.doi.org/10.3402/jev.v4.27066. - DOI - PMC - PubMed
1. Kim DK, Lee J, Kim SR, Choi DS, Yoon YJ, Kim JH, et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics. 2015;31:933–9. - PMC - PubMed
1. Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97:329–39. - PMC - PubMed
1. Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33:967–78. - PubMed

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373–83. - PMC - PubMed

[2] Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373–83. - PMC - PubMed

[3] Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4 27066, doi: http://dx.doi.org/10.3402/jev.v4.27066. - DOI - PMC - PubMed

[4] Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4 27066, doi: http://dx.doi.org/10.3402/jev.v4.27066. - DOI - PMC - PubMed

[5] Kim DK, Lee J, Kim SR, Choi DS, Yoon YJ, Kim JH, et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics. 2015;31:933–9. - PMC - PubMed

[6] Kim DK, Lee J, Kim SR, Choi DS, Yoon YJ, Kim JH, et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics. 2015;31:933–9. - PMC - PubMed

[7] Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97:329–39. - PMC - PubMed

[8] Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97:329–39. - PMC - PubMed

[9] Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33:967–78. - PubMed

[10] Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33:967–78. - PubMed

Account

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Affiliations

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Authors

Affiliations

Abstract

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials