Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine
Penn collection
Degree type
Discipline
Subject
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
Dentistry
Oral and Maxillofacial Surgery
Oral Biology and Oral Pathology
Other Dentistry
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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.