# Generation of four-chambered hearts through organoid fusions

> **NIH NIH DP2** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $1,404,480

## Abstract

Project Summary
Congenital heart defects (CHDs) account for 1-2% of all live births in the U.S. More than 90% of these
diseases are attributed to defects in heart valves and septum; Of which, few have been modeled in mice likely
due to species differences and genetic complexities behind the disease. As an alternative approach, human
induced pluripotent stem cells (hiPSC), which has demonstrated great success in mimicking other diseases,
falls short in the modeling of CHDs, especially in regard to spatial sensitive mechanisms like those involved in
heart chamber development. However, with the emergence of organoids, the field is making significant strides
toward better CHD models. Currently, the limitations of using organoids resides in the structures integrity when
compared to the endogenous tissue, yet, the potential for CHD modelling is unmatched. Here I propose using
a novel method based on the organoid fusion principle to generate hearts with anatomically features:
chambers, valves and septum. To do this, we will first fuse one atrial and one ventricular organoid to create the
cardiac valves. Next, we will further extend this process to advance the formation of the valves and begin
formation of the septum by fusing two atrial and two ventricular organoids. Furthermore, we plan to use several
of our hiPSC lines either carrying CHD mutations or being directly reprogrammed from patients diagnosed with
CHDs to generate fused organoids that will allow us to model the disease progressions in patients. We
anticipate that the successful application of these techniques will offer significant improvements in modeling
the normal human heart development and congenital heart defects, with the ultimate goal of preventing and
treating congenital heart diseases.

## Key facts

- **NIH application ID:** 10241678
- **Project number:** 1DP2HL163745-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Guang Li
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,404,480
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241678

## Citation

> US National Institutes of Health, RePORTER application 10241678, Generation of four-chambered hearts through organoid fusions (1DP2HL163745-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241678. Licensed CC0.

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