# Myofibroblast mediated mechanisms of fibrotic tendon healing

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2021 · $46,036

## Abstract

This F31 fellowship application outlines the training and research plan that will prepare Jessica Ackerman for a
future career as an independent investigator with expertise in sophisticated imaging of fibrotic pathologies.
Tendon injuries represent a large clinical burden, and healing often results in impaired restoration of mechanical
properties. Healing of the tendon occurs through a scar-mediated process that is not well understood, leading
to a lack of therapeutic targets. Currently no biological therapy is in use clinically to attenuate scarring following
tendon injury. Myofibroblasts play a key role in pathological fibrosis, primarily through excessive deposition of
matrix at the site of injury. Although there is evidence of myofibroblast involvement in tendon healing, their
contribution to the process has yet to be investigated in detail. We have shown previously that resident tendon
cells (tenocytes) differentiate to myofibroblasts during healing. Additionally, we have observed a decrease in
myofibroblast content in a model of regenerative tendon healing, as well as alterations in macrophage presence
and polarization. Macrophage-myofibroblast cross talk has been implicated in fibrosis in a number of other
tissues, and Mφ-polarization state may affect the eventual outcome of healing. Thus, our central hypothesis is
that Mφ-myofibroblast/tenocyte crosstalk is critical for tenocyte differentiation to myofibroblasts, and that
inducible depletion of myofibroblasts following tendon injury will attenuate scar formation and improve tendon
healing. To assess the presence and persistence of myofibroblasts and the effects of myofibroblast depletion,
we will use Postn-CreER to drive recombination of the Ai9 fluorescent reporter or ROSA-DTA construct,
respectively in activated myofibroblasts (Aim 1). Mice will undergo our well-established murine model of tendon
injury, involving complete transection and repair of the flexor digitorum longus (FDL) tendon in the hindpaw. The
temporal and molecular profile of the phenotypic shift of tenocytes to myofibroblasts will be defined in vitro (Aim
2A). Further, we will explore crosstalk between tenocytes/myofibroblasts and macrophages. Data suggests that
paracrine signaling via macrophages, specifically the M1 phenotype, is sufficient to drive myofibroblast
differentiation, which we will test with tenocytes in vitro (Aim 2B). Lastly, we plan to examine the effect of
differentiated myofibroblasts on macrophage polarization and function in vitro to establish how each cell type
may impact the other during the healing process (Aim 2C). Overall we plan to use the data from performing these
studies to inform our approach towards the goal of establishing a viable biological therapy to treat scarring
following tendon injury.

## Key facts

- **NIH application ID:** 10300005
- **Project number:** 5F31AR077398-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Jessica Eve Ackerman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300005

## Citation

> US National Institutes of Health, RePORTER application 10300005, Myofibroblast mediated mechanisms of fibrotic tendon healing (5F31AR077398-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10300005. Licensed CC0.

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