Osteoarthritis (OA) is a disabling, degenerative disease that involves every tissue in the joint. The inflammatory environment surrounding these tissues is believed to fundamentally underlie OA pathogenesis and may therefore hold a key to treatment. One prominent end result of this dysregulated inflammatory state is long- term, progressive cartilage tissue degradation. Effective disease modifying treatments that can intervene in this degradative cascade are not currently available. Human mesenchymal stem cell (hMSC) injections are emerging as a potential disease modifying treatment for OA due to their multi-faceted immunomodulatory properties. However, hMSC injections suffer from substantial variability in efficacy which can be attributed in part to the inherent complexity of using cells which contain significant population heterogeneity/cell states with varying levels of senescence. We therefore propose: 1) to develop a therapy based on hMSCs enriched for electrical properties associated with superior stemness and immunomodulatory/regenerative capacity and 2) to assess the therapeutic potential of these electrically enriched hMSCs using an in vitro model of early inflammatory OA. We envision that electrical enrichment can be implemented as a novel component of hMSC therapy for combating inflammation and promoting regeneration in OA.

Public Health Relevance

Despite osteoarthritis being a major cause of disability throughout the world, limited disease modifying treatments are currently available for patients. Adult mesenchymal stem cell injections are emerging as a potential disease modifying treatment yet still suffer from inconsistent clinical outcomes. We propose to improve efficacy of stem cell therapy through isolating specific stem cell subpopulations that may be superior at combating inflammatory osteoarthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG064550-02
Application #
9971444
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Williams, John
Project Start
2019-07-15
Project End
2021-04-30
Budget Start
2020-06-01
Budget End
2021-04-30
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Rensselaer Polytechnic Institute
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
002430742
City
Troy
State
NY
Country
United States
Zip Code
12180