Universität zu Köln

Burkert, Karsten, Taheri, Hadiseh, Hamad, Sarkawt, Oliverio, Matteo, Peinkofer, Gabriel, Kornfeld, Jan-Wilhelm, Harnying, Wacharee, Pfannkuche, Kurt, Hescheler, Juergen, Berkessel, Albrecht and Saric, Tomo (2021). Salicylic diamines selectively eliminate residual undifferentiated cells from pluripotent stem cell-derived cardiomyocyte preparations. Sci Rep, 11 (1). BERLIN: NATURE RESEARCH. ISSN 2045-2322

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Abstract

Clinical translation of pluripotent stem cell (PSC) derivatives is hindered by the tumorigenic risk from residual undifferentiated cells. Here, we identified salicylic diamines as potent agents exhibiting toxicity to murine and human PSCs but not to cardiomyocytes (CMs) derived from them. Half maximal inhibitory concentrations (IC50) of small molecules SM2 and SM6 were, respectively, 9- and 18-fold higher for human than murine PSCs, while the IC50 of SM8 was comparable for both PSC groups. Treatment of murine embryoid bodies in suspension differentiation cultures with the most effective small molecule SM6 significantly reduced PSC and non-PSC contamination and enriched CM populations that would otherwise be eliminated in genetic selection approaches. All tested salicylic diamines exerted their toxicity by inhibiting the oxygen consumption rate (OCR) in PSCs. No or only minimal and reversible effects on OCR, sarcomeric integrity, DNA stability, apoptosis rate, ROS levels or beating frequency were observed in PSC-CMs, although effects on human PSC-CMs seemed to be more deleterious at higher SM-concentrations. Teratoma formation from SM6-treated murine PSC-CMs was abolished or delayed compared to untreated cells. We conclude that salicylic diamines represent promising compounds for PSC removal and enrichment of CMs without the need for other selection strategies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Burkert, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Taheri, Hadiseh UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamad, Sarkawt UNSPECIFIED UNSPECIFIED UNSPECIFIED Oliverio, Matteo UNSPECIFIED UNSPECIFIED UNSPECIFIED Peinkofer, Gabriel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kornfeld, Jan-Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Harnying, Wacharee UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfannkuche, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Berkessel, Albrecht UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-573197
DOI:	10.1038/s41598-021-81351-z
Journal or Publication Title:	Sci Rep
Volume:	11
Number:	1
Date:	2021
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TERATOMA FORMATION; DIFFERENTIATION; TUMORIGENICITY; INHIBITION; SURVIVAL; THERAPY; PURIFICATION; METABOLISM; EFFICIENT; APOPTOSIS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57319