Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair

作者全名："Zhang, Yuxin; Luo, Wenping; Zheng, Liwen; Hu, Jing; Nie, Li; Zeng, Huan; Tan, Xi; Jiang, Yucan; Li, Yeming; Zhao, Tianyu; Yang, Zhuohui; He, Tong-Chuan; Zhang, Hongmei"

作者地址："[Zhang, Yuxin; Luo, Wenping; Zheng, Liwen; Hu, Jing; Nie, Li; Zeng, Huan; Tan, Xi; Jiang, Yucan; Li, Yeming; Zhao, Tianyu; Yang, Zhuohui; Zhang, Hongmei] Chongqing Med Univ, Affiliated Hosp Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, 426 Songshibei Rd, Chongqing 401147, Peoples R China; [Zhang, Yuxin; Zheng, Liwen; Hu, Jing; Zeng, Huan; Tan, Xi; Jiang, Yucan; Li, Yeming; Yang, Zhuohui; Zhang, Hongmei] Chongqing Med Univ, Affiliated Hosp Stomatol, Dept Pediat Dent, Chongqing, Peoples R China; [Luo, Wenping; Nie, Li; Zhao, Tianyu] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [He, Tong-Chuan] Univ Chicago, Med Ctr, Dept Orthopaed Surg & Rehabil Med, Mol Oncol Lab, Chicago, IL 60637 USA"

通信作者："Zhang, HM (通讯作者)，Chongqing Med Univ, Affiliated Hosp Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, 426 Songshibei Rd, Chongqing 401147, Peoples R China."

来源：STEM CELL RESEARCH & THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000904982000004

JCR分区：Q1

影响因子：7.5

年份：2022

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Bone defect; Human dental mesenchymal stem cells (hDMSCs); BMP9; Decellularized bone matrix (DBM) construct; Intrabony defect repair model

摘要："Background: BMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system. Methods: Intrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H & E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs. Results: BMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs. Conclusions: The reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies."

基金机构："National Natural Science Foundation of China; Natural Science Foundation of Chongqing [81870758, 32070539]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [cstc2021jcyjmsxmX0560]; [KJZD-K201900402]"

基金资助正文："The reported work was supported in part by research grants from the National Natural Science Foundation of China (#81870758 to HZ, #32070539 to WL), Natural Science Foundation of Chongqing (#cstc2021jcyjmsxmX0560 to HZ) and Scientific and Technological Research Program of Chongqing Municipal Education Commission (#KJZD-K201900402 to TZ)."