Generation of two human induced pluripotent stem cell lines from peripheral blood mononuclear cells of clozapine-tolerant and clozapine-induced myocarditis patients with treatment-resistant schizophrenia

Nazanin Vaziri; Diogo Marques; Xuemei Wang; Pranav Machiraju; Ankita Narang; Katerina Vlahos; Christos Pantelis; Steven C Greenway; Chad A Bousman

doi:10.1016/j.scr.2022.102877

Generation of two human induced pluripotent stem cell lines from peripheral blood mononuclear cells of clozapine-tolerant and clozapine-induced myocarditis patients with treatment-resistant schizophrenia

Stem Cell Res. 2022 Aug:63:102877. doi: 10.1016/j.scr.2022.102877. Epub 2022 Jul 28.

Authors

Nazanin Vaziri¹, Diogo Marques², Xuemei Wang³, Pranav Machiraju⁴, Ankita Narang⁵, Katerina Vlahos⁶, Christos Pantelis⁷, Steven C Greenway⁸, Chad A Bousman⁹

Affiliations

¹ Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
² Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁴ The University of Sydney, School of Medicine, Sydney, Australia.
⁵ Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁶ Murdoch Children's Research Institute, Parkville, Australia.
⁷ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Melbourne, VIC, Australia.
⁸ Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁹ Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Melbourne, VIC, Australia; Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: chad.bousman@ucalgary.ca.

PMID: 35917601
DOI: 10.1016/j.scr.2022.102877

Abstract

Clozapine has superior efficacy in the treatment of refractory schizophrenia; however, use of clozapine is limited due to severe side effects, including myocarditis. Using non-integrative Sendai virus, we generated induced pluripotent stem cell lines from peripheral blood mononuclear cells of two patients with refractory schizophrenia, one clozapine-tolerant and one clozapine-induced myocarditis. Both cell lines exhibited a normal karyotype and pluripotency was validated by flow cytometry, immunofluorescence and their ability to differentiate into the three germ layers. These lines can be used to generate 2D and 3D patient-specific human cellular models to identify the mechanism by which clozapine induces myocardial inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antipsychotic Agents* / adverse effects
Cell Differentiation
Clozapine* / adverse effects
Humans
Induced Pluripotent Stem Cells* / metabolism
Leukocytes, Mononuclear / metabolism
Myocarditis* / chemically induced
Schizophrenia* / drug therapy
Schizophrenia* / metabolism
Schizophrenia, Treatment-Resistant

Substances

Antipsychotic Agents
Clozapine