# Engineering Vascularized Cardiac Muscle

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $612,859

## Abstract

ABSTRACT
Cardiac muscle generated from human induced pluripotent stem cells (iPSCs) is being
increasingly used to model heart injury and regeneration. The lack of maturity, multicellular
composition, perfusable vasculature and patient specificity remain the key limitations of currently
available cardiac tissue models. Several advances, achieved in our labs during the previous grant
cycle, form the basis for the proposed patient specific studies of viral myocarditis and ischemia-
reperfusion injury: (i) Derivation of multiple cell types that compose native myocardium (cardiac
myocytes, cardiac fibroblasts, endothelial cells, mesenchymal stromal cells, circulating and
resident macrophages), all from the same starting human iPSCs for biological complexity and
patient specificity. (ii) Perfusable microvascular networks serving as a template for engineering
vascularized cardiac muscle. (iii) Ability to link tissues by vascular perfusion in a way allowing the
maintenance of the individual tissue niches while enabling cross-talk by circulating cells,
extracellular vesicles (EVs) and secreted factors. (iv) Development of an isogenic model of bone
marrow, serving as a source of immune cells when linked to the cardiac muscle by vascular flow.
(v) Models of viral myocarditis and ischemia-reperfusion injury, with data indicating the sex
specificity and therapeutic effects of EVs. We propose to build upon these advances and
bioengineer patient-specific vascularized human cardiac microbundles to study the individual
differences under normal conditions, and following the viral myocarditis, ischemic injury and EV
treatment. We hypothesize that the vascularized cardiac muscle of such a high maturity and
biological fidelity will be able to capture sex-specific responses to cardiac injury. To test this
hypothesis, we propose three specific aims that will be pursued in an integrated fashion, with the
outcomes of each aim informing the other two aims. Aim 1 is to engineer multicellular, patient-
specific, vascularized cardiac microbundles. Aim 2 is to deploy vascularized cardiac microbundles
in modeling acute viral myocarditis, for which males are at a higher risk. Aim 3 is to deploy
vascularized cardiac microbundles in modeling acute and sustained ischemia-reperfusion injury,
with females are at a higher risk. For both Aim 2 and Aim 3, we will also study the cell-protective
measures of EVs and miRNAs in their cargo. We believe that this work will have impact on both
the biological research and the treatment of heart injury and disease.

## Key facts

- **NIH application ID:** 10827975
- **Project number:** 5R01HL076485-17
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Gordana Vunjak-Novakovic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $612,859
- **Award type:** 5
- **Project period:** 2005-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827975

## Citation

> US National Institutes of Health, RePORTER application 10827975, Engineering Vascularized Cardiac Muscle (5R01HL076485-17). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10827975. Licensed CC0.

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