# Nanowired human cardiac spheroids for heart repair

> **NIH NIH R01** · CLEMSON UNIVERSITY · 2020 · $365,040

## Abstract

Project Summary: Cardiovascular disease is the leading cause of death and disability worldwide. Due to the
limited regenerative capacity of adult hearts, human induced pluripotent stem cells (hiPSCs) have received
significant attention due to their proven ability to derive functional cardiomyocytes (hiPSC-CMs). Despite the
progress, the current inability to effectively deliver and integrate hiPSC-CMs into damaged myocardium has
limited the applications of hiPSC technology in cardiac repair. The current strategies are limited by 1) low cell
retention and survival after cell transplantation, and 2) unspecific and immature phenotype of the current
hiPSC-CMs. To address these challenges, we pioneered the use of electrically conductive silicon nanowires
(e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids. The addition
of e-SiNWs was found to enhance electrical conduction in the spheroids and improve their function. In addition,
our recent publication showed electrical stimulation synergizes with e-SiNWs to promote ventricular lineage
specification and cellular maturation (i.e., ventricular maturation) and reduce the spontaneous beating of the
hiPSC cardiac spheroids in in vitro culture. Further, our in vivo studies showed the nanowired spheroids
improve cell retention and engraftment with host myocardium after transplantation, presumably due to their 3D
microtissue configuration and the e-SiNW enhanced electrical integration. Our long-term goal is to translate
nanowired hiPSC cardiac spheroid technology into a clinical therapy for heart repair. The goal of this
proposal is to 1) study the effects of the intrinsic (electrical and surface) properties of e-SiNWs and extrinsic
factor (electrical stimulation) on ventricular maturation of the nanowired spheroids, and 2) examine the effects
of ventricular maturity of the nanowired spheroids on their engraftment. The central hypothesis of this
proposal is the nanowired hiPSC cardiac spheroids provide a powerful platform to 1) accelerate ventricular
maturation of hiPSC-CMs in vitro and 2) improve the retention, engraftment and integration of hiPSC-CMs with
host myocardium in vivo. The proposal is innovative in that, for the first time, we prepare hiPSC cardiac
microtissues with defined ventricular maturity for transplantation. Accordingly, we will pursue three specific
aims: 1) Elucidate the mechanisms of the interactions between e-SiNWs and hiPSC-CMs, 2) Further advance
ventricular maturation of nanowired hiPSC cardiac spheroids through long-term electrical stimulations, and 3)
Examine in vivo efficacy of the nanowired hiPSC cardiac spheroids in both healthy (Aim 3a) and injured (Aim
3b) rat hearts. The completion of the proposed research would, for the first time, allow us to 1) produce
hiPSC-CMs with controlled ventricular maturity, 2) develop a set of quantitative criteria to assess ventricular
maturity of hiPSC-CMs for transplantation, and 3) identify a suitable ra...

## Key facts

- **NIH application ID:** 9933069
- **Project number:** 5R01HL133308-04
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Ying Mei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,040
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933069

## Citation

> US National Institutes of Health, RePORTER application 9933069, Nanowired human cardiac spheroids for heart repair (5R01HL133308-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933069. Licensed CC0.

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