MilliporeSigma
  • Tamoxifen treatment ameliorates contractile dysfunction of Duchenne muscular dystrophy stem cell-derived cardiomyocytes on bioengineered substrates.

Tamoxifen treatment ameliorates contractile dysfunction of Duchenne muscular dystrophy stem cell-derived cardiomyocytes on bioengineered substrates.

NPJ Regenerative medicine (2022-03-20)
Foster Birnbaum, Asuka Eguchi, Gaspard Pardon, Alex C Y Chang, Helen M Blau
ABSTRACT

Duchenne muscular dystrophy (DMD) is a progressive genetic myopathy that leads to heart failure from dilated cardiomyopathy by early adulthood. Recent evidence suggests that tamoxifen, a selective estrogen receptor modulator widely used to treat breast cancer, ameliorates DMD cardiomyopathy. However, the mechanism of action of 4-hydroxytamoxifen, the active metabolite of tamoxifen, on cardiomyocyte function remains unclear. To examine the effects of chronic 4-hydroxytamoxifen treatment, we used state-of-the-art human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and a bioengineered platform to model DMD. We assessed the beating rate and beating velocity of iPSC-CMs in monolayers and as single cells on micropatterns that promote a physiological cardiomyocyte morphology. We found that 4-hydroxytamoxifen treatment of DMD iPSC-CMs decreased beating rate, increased beating velocity, and ameliorated calcium-handling deficits, leading to prolonged viability. Our study highlights the utility of a bioengineered iPSC-CM platform for drug testing and underscores the potential of repurposing tamoxifen as a therapy for DMD cardiomyopathy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-OCT-4 [POU5F1] Antibody, clone 7F9.2, clone 7F9.2, from mouse