Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications

Kenneth W Witwer^{1

2}, Bas W M Van Balkom³, Stefania Bruno⁴, Andre Choo⁵, Massimo Dominici^{6

7}, Mario Gimona⁸, Andrew F Hill⁹, Dominique De Kleijn¹⁰, Mickey Koh^{11

12}, Ruenn Chai Lai¹³, S Alex Mitsialis¹⁴, Luis A Ortiz¹⁵, Eva Rohde⁸, Takashi Asada¹⁶, Wei Seong Toh¹⁷, Daniel J Weiss¹⁸, Lei Zheng¹⁹, Bernd Giebel²⁰, Sai Kiang Lim^{13

21}

Affiliations

¹ Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Division Internal Medicine and Dermatology, Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴ Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, Torino, Italy.
⁵ Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
⁶ MAB Laboratory, TPM of Mirandola, Mirandola, Italy.
⁷ Division of Oncology, University of Modena and Reggio Emilia, Modena, Italy.
⁸ GMP Laboratory, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Research Program Nanovesicular Therapies, Department of Transfusion Medicine and Celericon Therapeutics G.m.b.H., Paracelsus Medical University (PMU), Salzburg, Austria.
⁹ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia.
¹⁰ Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
¹¹ Department of Haematology, St George's University Hospital NHS Trust, London, UK.
¹² Cell Therapy Facility, Blood Services Group Health Sciences Authority, Singapore, Singapore.
¹³ Institute of Medical Biology, Agency for Science, Technology and Research, Singapore, Singapore.
¹⁴ Department of Pediatrics, Harvard Medical School & Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
¹⁵ Division of Environmental and Occupational Medicine, Department of Environmental and Occupational Health, Graduate School of Public Health at the University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Department of Tissue Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
¹⁷ Faculty of Dentistry, National University of Singapore, Singapore, Singapore.
¹⁸ Health Sciences Research Facility, University of Vermont College of Medicine, Burlington, VT, USA.
¹⁹ Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
²⁰ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²¹ Department of Surgery, YLL School of Medicine, National University of Singapore, Singapore, Singapore.

PMID: 31069028
PMCID: PMC6493293
DOI: 10.1080/20013078.2019.1609206

Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications

Kenneth W Witwer et al. J Extracell Vesicles. 2019.

. 2019 Apr 29;8(1):1609206.

doi: 10.1080/20013078.2019.1609206. eCollection 2019.

Authors

Affiliations

¹ Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Division Internal Medicine and Dermatology, Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴ Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, Torino, Italy.
⁵ Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
⁶ MAB Laboratory, TPM of Mirandola, Mirandola, Italy.
⁷ Division of Oncology, University of Modena and Reggio Emilia, Modena, Italy.
⁸ GMP Laboratory, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Research Program Nanovesicular Therapies, Department of Transfusion Medicine and Celericon Therapeutics G.m.b.H., Paracelsus Medical University (PMU), Salzburg, Austria.
⁹ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia.
¹⁰ Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
¹¹ Department of Haematology, St George's University Hospital NHS Trust, London, UK.
¹² Cell Therapy Facility, Blood Services Group Health Sciences Authority, Singapore, Singapore.
¹³ Institute of Medical Biology, Agency for Science, Technology and Research, Singapore, Singapore.
¹⁴ Department of Pediatrics, Harvard Medical School & Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
¹⁵ Division of Environmental and Occupational Medicine, Department of Environmental and Occupational Health, Graduate School of Public Health at the University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Department of Tissue Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
¹⁷ Faculty of Dentistry, National University of Singapore, Singapore, Singapore.
¹⁸ Health Sciences Research Facility, University of Vermont College of Medicine, Burlington, VT, USA.
¹⁹ Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
²⁰ Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²¹ Department of Surgery, YLL School of Medicine, National University of Singapore, Singapore, Singapore.

PMID: 31069028
PMCID: PMC6493293
DOI: 10.1080/20013078.2019.1609206

Abstract

Small extracellular vesicles (sEVs) from mesenchymal stromal/stem cells (MSCs) are transiting rapidly towards clinical applications. However, discrepancies and controversies about the biology, functions, and potency of MSC-sEVs have arisen due to several factors: the diversity of MSCs and their preparation; various methods of sEV production and separation; a lack of standardized quality assurance assays; and limited reproducibility of in vitro and in vivo functional assays. To address these issues, members of four societies (SOCRATES, ISEV, ISCT and ISBT) propose specific harmonization criteria for MSC-sEVs to facilitate data sharing and comparison, which should help to advance the field towards clinical applications. Specifically, MSC-sEVs should be defined by quantifiable metrics to identify the cellular origin of the sEVs in a preparation, presence of lipid-membrane vesicles, and the degree of physical and biochemical integrity of the vesicles. For practical purposes, new MSC-sEV preparations might also be measured against a well-characterized MSC-sEV biological reference. The ultimate goal of developing these metrics is to map aspects of MSC-sEV biology and therapeutic potency onto quantifiable features of each preparation.

Keywords: Definition; MSC; Please check whether the inserted Keywords are correct; Therapeutics; sEV.

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References

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Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications

Affiliations

Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications

Authors

Affiliations

Abstract

References

LinkOut - more resources

Full Text Sources

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