Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine

被引：65

作者：

Li, Yunsheng ^{[1
,2
]}

Xu, Junji ^{[1
]}

Mao, Lisha ^{[1
]}

Liu, Yi ^{[1
]}

Gao, Runtao ^{[1
]}

Zheng, Zongmei ^{[1
]}

Chen, Wanjun ^{[3
]}

Le, Anh ^{[4
]}

Shi, Songtao ^{[4
]}

Wang, Songlin ^{[1
,5
]}

机构：

[1] Capital Med Univ, Sch Stomatol, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Mol Lab Gene Therapy & Tooth Regenerat, Beijing 100050, Peoples R China

[2] Coal Gen Hosp, Dept Stomatol, Beijing, Peoples R China

[3] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, NIH, Bethesda, MD USA

[4] Univ So Calif, Ctr Craniofacial Mol Biol, Herman Ostrow Sch Dent, Los Angeles, CA 90089 USA

[5] Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100050, Peoples R China

来源：

STEM CELLS AND DEVELOPMENT | 2013年 / 22卷 / 14期

关键词：

HUMAN AQUAPORIN-1 CDNA; PIG PAROTID-GLANDS; STROMAL CELLS; MINIATURE PIG; ZOLEDRONIC ACID; FLUID SECRETION; TISSUE-REPAIR; DIFFERENTIATION; IMMUNOTHERAPY; MODEL;

D O I：

10.1089/scd.2012.0615

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页码：2047 / 2056

页数：10

共 26 条

[1]

American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws [J].