# Role of Perivascular Stem Cells in Ligament Healing and Regeneration

> **NIH VA IK2** · BALTIMORE VA MEDICAL CENTER · 2020 · —

## Abstract

Due to the physical demands placed on the knees and shoulders of service members, the incidence of
ligamentous injury is high in the Veteran population. These injuries have significant impact on Veterans’ quality
of life and ability to meet their occupational, recreational, and health goals. There is a need for better treatment
options to augment surgical repair or reconstruction for some of these ligament and tendon injuries. In
particular, 73% of massive rotator cuff tears fail to heal following surgical repair, and there are limited graft
options for anterior cruciate ligament (ACL) reconstruction. In order to address these shortcomings in current
surgical options, a biomimetic stem cell-based solution would be ideal.
Our approach to this problem is inspired by the body’s own ability to heal after injury. While poorly-vascularized
intra-articular ligament injuries such as ACL tears do not heal, well-vascularized extra-articular ligaments such
as the medial collateral ligament (MCL) can heal without operative intervention. The exact mechanisms behind
this observation are not well-understood. We hypothesize that a major difference between ligament healing
and non-healing is access to vascular supply, specifically, vascular-associated mesenchymal stem cells.
Pericytes are perivascular stem cell (PSC) population that is associated with blood vessels throughout the
body. Studies on tendon remodeling have postulated that pericytes from the tendon sheath are responsible for
neo-tendon formation in the event of tendon injury. However, these reports do not provide any empiric
evidence to support this hypothesis. It is our goal to provide definitive evidence of this hypothesis by using a
lineage tracing mouse model and a model of pericyte ablation to systematically establish the role that pericytes
play during ligament healing. We further propose to evaluate the efficacy of using human pericytes to treat
injuries to fibrous tissues such as the MCL and for a tissue-engineered ACL graft. Regardless of whether
pericytes directly contribute to ligament healing, they remain an attractive clinical option due to ease of
isolation and likely trophic effects. Our over-arching goal is to establish a basic science mechanism and proof
of concept for PSC-based therapies for ligament and tendon injuries. The overall hypothesis of this highly
clinically relevant proposal is that pericytes contribute to extra-articular ligament healing; and that exogenous
PSC-based therapies can enhance healing in both intra-articular and extra-articular ligament injuries.
If successful, these studies would collectively establish the foundation for new pericyte-based therapies to treat
ligament injuries that are unfortunately very common in Veterans. Specifically, these would include both
injections to promote the non-operative healing of extra-articular ligament injuries such as MCL sprains,
adjunct therapy for surgical treatment of tendon and ligament tears such as rotator cuff injur...

## Key facts

- **NIH application ID:** 9890865
- **Project number:** 1IK2BX004879-01
- **Recipient organization:** BALTIMORE VA MEDICAL CENTER
- **Principal Investigator:** Natalie L Leong
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890865

## Citation

> US National Institutes of Health, RePORTER application 9890865, Role of Perivascular Stem Cells in Ligament Healing and Regeneration (1IK2BX004879-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890865. Licensed CC0.

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