# Engineered Asymmetric Hydrogel for Muscle Stem Cell Polarity and Fate Specification

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $441,706

## Abstract

ABSTRACT
Skeletal muscle stem cell (MuSC) transplantation is emerging as a promising strategy for treating muscle-
associated trauma and diseases. However, MuSCs spontaneously lose their “stemness” and engraftment
potential in conventional 2D culture, critically limiting their applicability for cell-based therapy. This inability to
culture MuSCs further limits the employment of cell engineering strategies, such as ex vivo gene editing patient
derived cells. Thus, there is a critical need for a strategy to maintain and expand therapeutically potent MuSC
ex vivo long-term. To date, MuSC culture systems that recapitulate the asymmetric MuSC niche, consisting of
myofiber and basal lamina, required to establish cellular polarity, support physiologic cell division, and guide
fate specification, do not exist. The contribution of active mechanical forces in modulating MuSC polarity,
division, and fate specification also remains overlooked. We believe that establishing MuSC polarity is a
requirement for supporting long-term symmetric expansion ex vivo through biochemical and biophysical means.
To this end, the proposed research will engineer an asymmetric designer platform for expanding self-renewing
MuSCs ex vivo long-term by directing cellular polarity and fate specification. In Aim 1, we will identify minimally
essential asymmetric cues for establishing MuSC polarity by engineering an asymmetric hydrogel. In Aim 2, we
will determine the effects of biochemically promoting symmetric cell division on long-term expansion of MuSCs
using the asymmetric hydrogel. Biochemical strategies to inhibit asymmetric division and to promote symmetric
division to achieve ex vivo MuSC expansion will be tested. In Aim 3, we will determine the effects of dynamic
biomechanical stretch on regulation of symmetric MuSC expansion using the asymmetric hydrogel.
Mechanisms by which externally applied forces align mitotic spindle orientation and regulate cell division of
polarized MuSCs will be tested. Successful outcomes of this research will not only develop a platform for
expanding MuSCs for cell therapies by directing stem cell polarity and fate specification but also provide
establish a new paradigm for harnessing stem cell polarity in cell-instructive biomaterials for regenerative
medicine.

## Key facts

- **NIH application ID:** 10765743
- **Project number:** 5R01AR080616-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Woojin Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,706
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765743

## Citation

> US National Institutes of Health, RePORTER application 10765743, Engineered Asymmetric Hydrogel for Muscle Stem Cell Polarity and Fate Specification (5R01AR080616-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10765743. Licensed CC0.

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