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

Pogozhykh, Denys
; 
Eicke, Dorothee
; 
Gryshkov, Oleksandr
; 
Wolkers, Willem F
; ; 
Guzmán, Carlos A
; 
Blasczyk, Rainer
; 
Figueiredo, Constança
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Issue Date
2020-10-16
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Abstract
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.
Citation
Int J Mol Sci. 2020 Oct 16;21(20):7654. doi: 10.3390/ijms21207654.
Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Publisher
MDPI
Journal
International journal of molecular sciences
URI
http://hdl.handle.net/10033/622571
DOI
10.3390/ijms21207654
PubMed ID
33081128
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Article
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en
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1422-0067
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Attribution-NonCommercial-ShareAlike 4.0 International
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publications of the research group vaccinology and applied microbiology (VAC)