# A Novel Strategy of Endogenous Progenitor Cell Homing Using Exosomes for Condylar Fibrocartilage Repair in Temporomandibular Joint

> **NIH NIH R03** · UNIVERSITY OF IOWA · 2021 · $154,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Degenerative temporomandibular joint (TMJ) disorders (TMD) are some of the most challenging oral and
maxillofacial problems, and when left untreated, they eventually lead to significant functional deficits, pain,
stiffness, and osteoarthritis. As an example of degenerative TMD, the risk for post-traumatic osteoarthritis (PTOA)
after serious joint injuries has not improved substantially in the last 40 years despite many refinements in care.
This underscores the urgent need for new treatments to prevent PTOA initiated by joint damage. Fibrocartilage
is notoriously limited in its intrinsic capacity for repair, focal damage associated with joint injuries seldom heals
and often worsens to engulf entire articular surfaces. Cell-based therapies intended to regenerate neocartilage
in situ have shown some clinical promise. The two most common, microfracture and autologous chondrocyte
implantation (ACI), work well in the short term; however, long term results have been disappointing. The
presence of chondrogenic progenitor cells (CPCs) in the TMJ fibrocartilage suggests that a rudimentary self-
repair mechanism exists that might be marshaled for fibrocartilage regeneration after traumatic injury. CPC
recruitment can be enhanced by exosomes derived from bone marrow stromal cells (BMSC-Exos), which serve
an important role in intercellular communication and tissue repair.
 Our central hypothesis is that BMSC-Exos will stimulate TMJ condylar fibrocartilage repair by promoting
CPC chemotaxis and chondrogenesis, intended for the treatment of focal lesions in TMJ fibrocartilage. The main
appeal of a CPC-based repair strategy lies in their ability to heal by self-congregating at injury sites without ex
vivo cell expansion and the additional surgery needed for grafting in ACI. Specific aims in this proposed study
are to characterize BMSC-Exos and determine the effects of BMSC-Exos on CPC migration and fibrocartilage
differentiation in vitro. Finally, in vivo fibrocartilage repair will be evaluated in a rabbit TMJ disc perforation model,
where direct fibrocartilage contact between the condyle and mandibular fossa will induce degenerative
fibrocartilage. BMSC-Exos encapsulated in hydrogel (F-127/hyaluronic acid) will be injected to the damaged
TMJs 2 weeks after the perforation surgeries. Six weeks after the injection, integrity of the repaired fibrocartilage
will be determined by histological/immunohistochemical staining and evaluated based on a modified OARSI
scoring system. At the conclusion of this project, we will be able to define the therapeutic potential of BMSC-
Exos for fibrocartilage repair and to identify miRNAs that may regulate cell migration and neotissue formation.
 As our future research plans, we will validate the candidate key miRNAs and synthesize target microRNA
(miRNAs) for CPC migration and neofibrocartilage formation. The target miRNAs will be loaded in engineered
exosomes for in vivo delivery, thereby replacing BMSC ...

## Key facts

- **NIH application ID:** 10260595
- **Project number:** 5R03DE030166-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Kyungsup Shin
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $154,500
- **Award type:** 5
- **Project period:** 2020-09-10 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260595

## Citation

> US National Institutes of Health, RePORTER application 10260595, A Novel Strategy of Endogenous Progenitor Cell Homing Using Exosomes for Condylar Fibrocartilage Repair in Temporomandibular Joint (5R03DE030166-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10260595. Licensed CC0.

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