316 - Generation of Human Heart Organoids to Study the Effect of Maternal Diabetes on Fetal Heart Development and the Cardioprotective Effects of DHA

Poster Board #: 316
Publication #: 3906-HP-QA.316

Background: Diabetes in pregnancy is associated with an increased risk of fetal cardiac complications. In the first trimester, maternal hyperglycemia can cause diabetic embryopathy resulting in major birth defects and spontaneous abortions, Diabetic fetopathy occurs in the second and third trimesters, resulting in fetal hyperglycemia, hyperinsulinemia, and macrosomia. Hyperglycemia in diabetic mothers enhances the risk of fetal cardiac hypertrophy during pregnancy. However, the mechanism of high-glucose-induced cardiac hypertrophy is not largely understood.


Objective: Cardiac organoids generated from human induced pluripotent stem cell (iPSC) were used to study the effect of high glucose and insulin on the developing heart. Potential therapeutic cardioprotective effect of DHA (Docosahexaenoic acid) on the developing heart in maternal diabetes is in progress.


Design/Methods: We established and characterized high glucose versus normal glucose organoid model. We studied cellular morphological features as hypertrophy by Immunofluorescence markers. Analysis of gene expression by RNA-Sequencing and evaluation of the effect of DHA exposure on high glucose organoids will be studied.


Results: Under the light microscope there was increase in the size of high glucose vs the normal glucose organoids (Fig. 1). Using confocal microscopy images there was an increase in cardiomyocytes number by using TNNT2 as a cardiomyocyte marker, increase in the epicardial cell number by using WT1 which is an epicardial cell marker and increase in the number of nuclei (indicator of increase the cell number) using DNA stain (DAPI) in high versus normal glucose organoids (Fig. 2). MEA (microelectrode array) recordings showed arrhythmias in the high versus normal glucose organoids (Fig. 3).

Conclusion(s): The aim of this study was to investigate the mechanism of hyperglycemia induced cardiac hypertrophy during cardiogenesis. We demonstrated that there was an increased organoid size, cardiomyocytes numbers, epicardial cell number in high versus normal glucose organoids. Using MEA (microelectrode array) recordings showed arrhythmias in the high versus normal glucose organoids. Study the gene expression and cardioprotective effect of DHA in the high versus normal glucose organoid are in progress.

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Authors/Institutions: Mishref M. Abdelhamid, Michigan State University College of Human Medicine, East Lansing, Michigan, United States; Yonatan R. Lewis-Israeli, Michigan State University College of Human Medicine, East Lansing, Michigan, United States; Amanda Huang, Michigan State University College of Human Medicine, East Lansing, Michigan, United States; Aitor Aguirre, Michigan State University College of Human Medicine, East Lansing, Michigan, United States