Current state-of-the-art treatment of rheumatoid arthritis (RA) is not curative and is associated with considerable toxicity. Bone erosion and cartilage damage are the most severe complications of RA and the major reasons for pain and disability in this disease. They are also key targets that are resistant to current therapies. Substantial evidence now exists that mesenchymal stem cells (MSC) have regeneration ability and immunomodulatory functions that could contribute to treatment of autoimmune diseases. Nonetheless, it is unknown whether MSC, particularly those derived from gingival tissues (GMSC) can directly affect bone and cartilage protection. Based on our preliminary observations, we make a bold hypothesis that GMSC can directly inhibit the formation of osteoclasts and activities of inflamed synovial tissues and through these mechanisms can prevent bone erosion and cartilage damage in rheumatoid arthritis. The study will include two phases (R61 and R33) with three specific aims. For the R61 phase, specific aim 1 and 2 will test the hypothesis that GMSC suppress osteoclast differentiation and activities, as well as activation and function of inflamed synovial tissues in the in vitro and in vivo with collagen-induced arthritis (CIA) model and in the R33 phase (Specific aim 3) a further validation will be conducted using a humanized model. When successfully completed, this project will help us understand the characteristics of GMSC in protecting bone erosion and cartilage damage in autoimmune arthritis and may lead to a potential therapeutic strategy for RA and other human autoimmune diseases.

Public Health Relevance

Joints destruction characterized by bone erosion and cartilage damage is a mostly severe consequence and key reason that is resistant to current therapies in patients with rheumatoid arthritis. In the current study, we plan to use the collagen-induced arthritis and humanized animal models to study therapeutic effect of gingiva-derived mesenchymal stem cells (GMSC) on these models, particularly focusing on how GMSC suppress osteoclast differentiation/function and activities of inflamed synovial tissues in autoimmune arthritis, with the ultimate aim of improving therapeutic options for patients with RA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Project #
1R61AR073049-01
Application #
9468571
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Mao, Su-Yau
Project Start
2017-09-01
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033