# Cell Therapy in Hypertrophied and Remodeled Left Ventricle

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $628,744

## Abstract

Cell Therapy in Hypertrophied and Remodeled Left Ventricle
ABSTRACT
The recent report of increased arrhythmic potential in hearts of non-human primates that received cell therapy
causes serious concerns in field of cardiac stem cell therapy. Although the beneficial effects of human induced
pluripotent stem cell (hiPSC) cellular therapy in hearts with post myocardial infarction (MI) have been recently
reported in large animal studies, there could be additional benefits in applying a highly functional prefabricated
cardiac muscle tissue equivalent over the MI surface. The specific aims (SA) are: SA1. To fabricate the larger
and thicker human cardiac muscle patch (hCMP) using the hiPSC - cardiomyocytes (CM), - smooth muscle
cells (SMC) and – endothelial cells (EC). We will fabricate a new type of larger and thicker hCMP and
characterize its vascular, electrical, and mechanical properties in vitro. To increase the engraftment rate, we
will generate hiPSC lines by engineering the hiPSC, in which human HLA Class I and/or Class II protein
expression have been knocked out (HLA-KO -hCMP) by the gene editing technology. To reduce the
arrhythmogenic potential, we will generate hiPSC lines by engineering the hiPSC to overexpress the gap
junction protein: Cx43 (Cx43-hCMP). SA2. Using an immuno-suppressed porcine model of post-infarction LV
remodeling, we will examine whether the transplantation of a prefabricated hCMP will result in better functional
outcomes in reductions in LV scar bulging and wall stress, and improvements in myocardial bioenergetics and
contractile function as compared to standard cell injection. We will compare the electrical stability of hearts
with or without hCMP transplantation by continuously monitoring ECG for 8 weeks in vivo, and by conducting
ex vivo dual optical mapping studies of electrical propagation. We will develop the completely non-invasive
NMR technology that will provide unprecedented levels of sensitivity and signal-to-noise ratio (SNR) for P-31
NMR spectroscopy measuring the myocardial ATP hydrolysis rate with a precision of micro moles/s per gram
of myocardium in a large bore magnet, which can be applied clinically. The findings of the studies will advance
our understanding of the mechanisms of functional benefits of cell therapy in hearts with post-infarction LV
remodeling, which can lead to better diagnostic and therapeutic modalities for CHF patients.

## Key facts

- **NIH application ID:** 9930107
- **Project number:** 5R01HL114120-09
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Jianyi Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $628,744
- **Award type:** 5
- **Project period:** 2012-08-10 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930107

## Citation

> US National Institutes of Health, RePORTER application 9930107, Cell Therapy in Hypertrophied and Remodeled Left Ventricle (5R01HL114120-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9930107. Licensed CC0.

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