# Using a Cardiac Microtissue System to Evaluate and Replicate Clinical Therapy Responses using Patient Cell-Derived Exosomes

> **NIH NIH R21** · TEXAS HEART INSTITUTE · 2020 · $203,750

## Abstract

Summary
Cell therapy for post-infarct cardiac repair has shown limited and mixed results, most likely due to patients'
individual cell characteristics or to the infarct environment experienced by the transplanted cells. Identifying the
potential molecular and cellular components that contribute to patient-specific responses and ways to minimize
the environmental stress on transplanted cells may lead to the development of new strategies for cardiac repair.
Additionally, numerous studies have shown that the effects of at least some cell-based therapies can be
attributed primarily to secreted cellular factors that are packaged inside exosomes. These exosomes are
considered critical mediators of intercellular information and play a direct role in injury-induced tissue repair
processes in multiple physiological systems. Our group is particularly interested in the characterization of
exosomes from cardiovascular disease patients who improved in a cell therapy study and in the utilization of
these exosome cargos in the development of tissue-engineered cardiac patches for optimal functional
myocardial repair. We are also interested in using our in vitro cardiac microtissue system as a testbed to evaluate
patient cell-exosome interactions and associations with clinical trial responses. We will derive bone marrow
mesenchymal stem cells (MSCs), MSC exosomes, and human induced pluripotent stem cells (hiPSCs) from
healthy individuals and patients in the Cardiovascular Cell Therapy Research Network (CCTRN)-FOCUS clinical
trial categorized as improvers at 6 months, [i.e., improved left ventricular ejection fraction, end-systolic volume
and maximal oxygen consumption], or as non-improvers (declined in the 3 outcomes). Cardiac microtissues,
containing cardiac cells derived from healthy control hiPSCs, cultured in native and infarct-like conditions will be
treated with improvers' exosomes. Changes in microtissue function, cardiomyocyte maturation, cell survival and
proliferation will be compared among improvers, placebo and non-improvers exosomes. Meanwhile, high
throughput assays will be used to identify differences in the exosome cargos of the top 3 clinical improvers and
non-improvers and correlated with in vitro responses. We expect that improver's exosomes will contain potent
beneficial factors to enhance cell and microtissue maturation and function under infarct-like stress. Next, patient-
specific microtissues containing hiPSC-derived cardiac cells generated from bone marrow of the top 3 improvers
and non-improvers will be treated with autologous or allogenic (improver, non-improver or, healthy) exosomes
under infarct-like conditions. By exposing patient-specific “infarcted” cardiac microtissues to autologous or
allogeneic exosomes, we can evaluate patient-specific cell-exosome interactions in a controlled in vitro setting
that mimics the clinical condition. Ultimately, these studies will provide new insights into cell-exosome
interactions in an infarct as ...

## Key facts

- **NIH application ID:** 9924691
- **Project number:** 5R21HL144244-02
- **Recipient organization:** TEXAS HEART INSTITUTE
- **Principal Investigator:** Camila Hochman-Mendez
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,750
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924691

## Citation

> US National Institutes of Health, RePORTER application 9924691, Using a Cardiac Microtissue System to Evaluate and Replicate Clinical Therapy Responses using Patient Cell-Derived Exosomes (5R21HL144244-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9924691. Licensed CC0.

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