Cardiac organoids: a model to investigate the effect of diabetes on cardiac development and function

Magdalini Eleftheriadou, Hojjat Naderi-Meshkin, Koray N. Potel, Wiwit Ananda Wahyu Setyaningsih, Andrew Yacoub, Alan W. Stitt, David J. Grieve, Andriana Margariti*

*Corresponding author for this work

Research output: Contribution to journalMeeting abstractpeer-review


Diabetes and associated cardiovascular diseases (CVDs) are a class of disorders affecting the heart or blood vessels. Despite progress in clinical research and therapy, CVDs still represent the leading cause of mortality and morbidity worldwide. The hallmarks of cardiac diseases include heart dysfunction and cardiomyocyte death, inflammation, fibrosis, scar tissue, hyperplasia, hypertrophy, and abnormal ventricular remodelling. The loss of cardiomyocytes is an irreversible process that leads to fibrosis and scar formation, which, in turn, induce heart failure with progressive and dramatic consequences. Both genetic and environmental factors pathologically contribute to the development of CVDs, but the precise causes that trigger cardiac diseases and their progression are still largely unknown. The lack of reliable human model systems for such diseases has hampered the unravelling of the underlying molecular mechanisms and cellular processes involved in heart diseases at their initial stage and during their progression. In this study we use induced pluripotent stem cells (iPSCs) from diabetic and non-diabetic donors to recapitulate an iPSC-driven cardiac model with the aim of underlining the potential of stem-cell biology-based approaches in the elucidation of the pathophysiology of cardiac disease.

Cardiomyocytes were generated from iPS cells from both diabetic (DiPSC-CMs) and non-diabetic donors (NDiPS-CMs) within a thirteen day differentiation protocol. Cardiac commitment was assessed by Flow cytometry, PCR analysis, and Immunofluorescence staining. Morphological features of the sarcomere arrangement and mitochondria size were assessed using TEM microscopy. Cardiac function was measured by assessing calcium flux using Flexstation. Beating qualities were assessed by Nikon 6D Life imaging.

Upon differentiation both DiPSC-CMs and NDiPSC-CMs presented strong cardiac commitment as evident by the significant expression of cardiac markers evaluated by PCR and flow cytometry. iPS-CM from both donors presented no significant differences in the expression of cardiac markers brachyury and cardiac troponin as assessed by flow cytometry (p > 0.7078) and sarcomere proteins a-Actinin, myosin light chain MLCA2 assessed by immunofluorescence staining. Cardiomyocytes derived from diabetic donors (DiPS-CMs) showed differences in the uptake of calcium when these compared to the nondiabetic counterparts (NDiPS-CMs). Calcium flux was measure by capturing fluorescence intensity of Fura-2 calcium dye by Flexstation (p > 0.0156). TEM imaging and assessment of mitochondria between DiPSC-CMs and NDiPS-CMs showed differences in mitochondrial morphological features such as aspect ratio, perimeter and length (p > 0.05) between our two groups indicating a morphological change that may underly be related to an underlying mitochondrial disorder associated to a metabolic dysfunction.

Original languageEnglish
Issue numberSuppl 3
Publication statusPublished - 02 Jun 2023
EventBritish Cardiovascular Society Annual Conference 2023 - Manchester, United Kingdom
Duration: 05 Jun 202307 Jun 2023


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