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Article

Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV)

1
Institute of Molecular and Cellular Biology, A*STAR, 8A Biomedical Grove, Singapore 138648, Singapore
2
Bioprocessing Technology Institute, A*STAR, 20 Biopolis Way, Singapore 138668, Singapore
3
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore (NUS), 9 Engineering Drive 1, Singapore 117575, Singapore
4
Department of Surgery, YLL School of Medicine, National University of Singapore (NUS), 5 Lower Kent Ridge Road, Singapore 119074, Singapore
*
Author to whom correspondence should be addressed.
Academic Editors: Samir E.L. Andaloussi, Joel Nordin, André Görgens and Daniel W. Hagey
Pharmaceuticals 2021, 14(4), 345; https://doi.org/10.3390/ph14040345
Received: 4 March 2021 / Revised: 29 March 2021 / Accepted: 7 April 2021 / Published: 9 April 2021
Mesenchymal-stem/stromal-cell-derived small extracellular vesicles (MSC-sEV) have been shown to ameliorate many diseases in preclinical studies. However, translating MSC-sEV into clinical use requires the development of scalable manufacturing processes for highly reproducible preparations of safe and potent MSC-sEVs. A major source of variability in MSC-sEV preparations is EV producer cells. To circumvent variability in producer cells, clonal immortalized MSC lines as EV producer lines are increasingly being used for sEV production. The use of sEVs from immortalized producer cells inevitably raises safety concerns regarding the tumorigenicity or tumor promoting potential of the EV products. In this study, cells from E1-MYC line, a MSC cell line immortalized with the MYC gene, were injected subcutaneously into athymic nude mice. At 84 days post-injection, no tumor formation was observed at the injection site, lungs, or lymph nodes. E1-MYC cells pre-and post-sEV production did not exhibit anchorage-independent growth in soft agar. Daily intraperitoneal injections of 1 or 5 μg sEVs from E1-MYC into athymic nude mice with FaDu human head and neck cancer xenografts for 28 days did not promote or inhibit tumor growth relative to the xenograft treated with vehicle control. Therefore, MYC-immortalized MSCs are not tumorigenic and sEVs from these MSCs do not promote tumor growth. View Full-Text
Keywords: mesenchymal stem/stromal cell; small extracellullar vesicles; tumorigenicity mesenchymal stem/stromal cell; small extracellullar vesicles; tumorigenicity
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MDPI and ACS Style

Tan, T.T.; Lai, R.C.; Padmanabhan, J.; Sim, W.K.; Choo, A.B.H.; Lim, S.K. Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV). Pharmaceuticals 2021, 14, 345. https://doi.org/10.3390/ph14040345

AMA Style

Tan TT, Lai RC, Padmanabhan J, Sim WK, Choo ABH, Lim SK. Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV). Pharmaceuticals. 2021; 14(4):345. https://doi.org/10.3390/ph14040345

Chicago/Turabian Style

Tan, Thong T., Ruenn C. Lai, Jayanthi Padmanabhan, Wei K. Sim, Andre B.H. Choo, and Sai K. Lim. 2021. "Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV)" Pharmaceuticals 14, no. 4: 345. https://doi.org/10.3390/ph14040345

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