# Stem cell-based tissue engineering for myotendinous junction modeling and repair

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $331,392

## Abstract

PROJECT SUMMARY/ABSTRACT
Myotendinous junctions are the direct interface between muscle and tendon and the affected site in
traumatic
muscle injury and myotendinous rupture. Given the inconsistent effectiveness of existing treatments for
myotendinous injuries, we propose developing an alternative approach using human induced pluripotent stem
cells (iPSCs). Such cells have the capacity to create progenitor cells that can contribute to muscle and tendon
regeneration. Our specific goals of this study are to engineer iPSC-derived muscle-tendon units and evaluate
their utility as an in vitro model to study myotendinous junction formation, and to repair damages in muscle,
tendon, and myotendinous junctions. The fundamental hypothesis guiding this proposal is that iPSC-derived
musculoskeletal progenitor cells (skeletal muscle progenitor cells and tendon progenitor cells) will interact with
each other and form a muscle-tendon unit with functional myotendinous junctions. This hypothesis is supported
by our published studies and preliminary data demonstrating the feasibility of producing human musculoskeletal
tissues from iPSCs. In this proposal, we will prepare lines of human tendon progenitor cells (hTPCs) from iPSCs.
The established cells will be co-cultured with iPSC-derived skeletal muscle progenitor cells (hSMPCs) using
newly featured cell culture systems for iPSCs, two-dimensional micropatterned culture platforms (Aim 1).
Topographical and molecular guidance from the micropatterns can simulate cellular and molecular complexity
in musculoskeletal development and pathology. Next, we will create three-dimensional muscle-tendon tissue
cultures using iPSC-derived musculoskeletal progenitor cells and analyze their anatomical and physiological
properties to extend the utility of iPSCs for modeling myotendinous junction formation (Aim 2). Throughout the
development of these 3D culture models, we hope to identify the roles of exogenous stimulations such as
signaling molecules and mechanical loads for muscle-tendon differentiation and myotendinous junction
formation. Lastly, we will test the capacity of iPSC-derived muscle-tendon tissues to regenerate injured muscle,
tendon, and myotendinous junctions by studying implantation in a rat model of complete myotendinous junction
rupture (Aim 3). These aims will provide highly novel insights into effective approaches using iPSC-based in vitro
modeling and treatments. As iPSCs can now be derived from human adult somatic tissues, this approach can
be used to develop patient-specific, cell-based in vitro models and therapy for human disease. The results of
this project will accelerate progress towards effective treatments for patients with musculoskeletal disorders.
Given the lack of effective treatments for myotendinous injuries and the consequential burden it places on
society, this study is both urgent and timely.

## Key facts

- **NIH application ID:** 10128387
- **Project number:** 5R01AR077191-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Masatoshi Suzuki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $331,392
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128387

## Citation

> US National Institutes of Health, RePORTER application 10128387, Stem cell-based tissue engineering for myotendinous junction modeling and repair (5R01AR077191-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10128387. Licensed CC0.

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