Departmental Papers (Dental)
Title
Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine
Document Type
Journal Article
Date of this Version
7-15-2013
Publication Source
Stem Cells and Development
Volume
22
Issue
14
Start Page
2047
Last Page
2056
DOI
10.1089/scd.2012.0615
Abstract
Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
Keywords
Animals, Biological Markers, Bisphosphonate-Associated Osteonecrosis of the Jaw, Diphosphonates, Disease Models, Animal, Female, Forkhead Transcription Factors, Humans, Imidazoles, Interleukin-17, Male, Mandible, Mesenchymal Stem Cell Transplantation, Swine, Swine, Miniature, T-Lymphocytes, Regulatory, Transplantation, Homologous, interleukin 17, zoledronic acid, allogeneic stem cell transplantation, allogeneic stem cell transplantation, animal experiment, animal model, animal tissue, apoptosis, article, bone tissue, cell culture, controlled study, female, flow cytometry, immunoregulation, jaw osteonecrosis, mesenchymal stem cell transplantation, minipig, nonhuman, priority journal, regulatory T lymphocyte, reverse transcription polymerase chain reaction
Recommended Citation
Li, Y., Xu, J., Mao, L., Liu, Y., Gao, R., Zheng, Z., Chen, W., Le, A., Shi, S., & Wang, S. (2013). Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine. Stem Cells and Development, 22 (14), 2047-2056. http://dx.doi.org/10.1089/scd.2012.0615
Included in
Oral and Maxillofacial Surgery Commons, Oral Biology and Oral Pathology Commons, Other Dentistry Commons
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
At the time of publication, author Ahn Le was affiliated with the Herman Ostrow School of Dentistry, University of Southern California. Currently, she is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Songtao Shi was affiliated with Herman Ostrow School of Dentistry, University of Southern California. Currently, he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.