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Article

Towards Reduction or Substitution of Cytotoxic DMSO in Biobanking of Functional Bioengineered Megakaryocytes

1
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, 30625 Hannover, Germany
2
Institute for Multiphase Processes, Leibniz Universität Hannover, 30823 Garbsen, Germany
3
Unit for Reproductive Medicine, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
4
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7654; https://doi.org/10.3390/ijms21207654
Received: 11 September 2020 / Revised: 5 October 2020 / Accepted: 14 October 2020 / Published: 16 October 2020
(This article belongs to the Section Molecular Toxicology)
Donor platelet transfusion is currently the only efficient treatment of life-threatening thrombocytopenia, but it is highly challenged by immunological, quality, and contamination issues, as well as short shelf life of the donor material. Ex vivo produced megakaryocytes and platelets represent a promising alternative strategy to the conventional platelet transfusion. However, practical implementation of such strategy demands availability of reliable biobanking techniques, which would permit eliminating continuous cell culture maintenance, ensure time for quality testing, enable stock management and logistics, as well as availability in a ready-to-use manner. At the same time, protocols applying DMSO-based cryopreservation media were associated with increased risks of adverse long-term side effects after patient use. Here, we show the possibility to develop cryopreservation techniques for iPSC-derived megakaryocytes under defined xeno-free conditions with significant reduction or complete elimination of DMSO. Comprehensive phenotypic and functional in vitro characterization of megakaryocytes has been performed before and after cryopreservation. Megakaryocytes cryopreserved DMSO-free, or using low DMSO concentrations, showed the capability to produce platelets in vivo after transfusion in a mouse model. These findings propose biobanking approaches essential for development of megakaryocyte-based replacement and regenerative therapies. View Full-Text
Keywords: megakaryocytes; platelets; induced pluripotent stem cells (iPSC); biobanking; cytotoxicity; mouse model; transfusion; dimethyl sulfoxide; propane-1,2-diol; ethylene glycol megakaryocytes; platelets; induced pluripotent stem cells (iPSC); biobanking; cytotoxicity; mouse model; transfusion; dimethyl sulfoxide; propane-1,2-diol; ethylene glycol
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MDPI and ACS Style

Pogozhykh, D.; Eicke, D.; Gryshkov, O.; Wolkers, W.F.; Schulze, K.; Guzmán, C.A.; Blasczyk, R.; Figueiredo, C. Towards Reduction or Substitution of Cytotoxic DMSO in Biobanking of Functional Bioengineered Megakaryocytes. Int. J. Mol. Sci. 2020, 21, 7654. https://doi.org/10.3390/ijms21207654

AMA Style

Pogozhykh D, Eicke D, Gryshkov O, Wolkers WF, Schulze K, Guzmán CA, Blasczyk R, Figueiredo C. Towards Reduction or Substitution of Cytotoxic DMSO in Biobanking of Functional Bioengineered Megakaryocytes. International Journal of Molecular Sciences. 2020; 21(20):7654. https://doi.org/10.3390/ijms21207654

Chicago/Turabian Style

Pogozhykh, Denys, Dorothee Eicke, Oleksandr Gryshkov, Willem F. Wolkers, Kai Schulze, Carlos A. Guzmán, Rainer Blasczyk, and Constança Figueiredo. 2020. "Towards Reduction or Substitution of Cytotoxic DMSO in Biobanking of Functional Bioengineered Megakaryocytes" International Journal of Molecular Sciences 21, no. 20: 7654. https://doi.org/10.3390/ijms21207654

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