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

Stem Cell Research & Therapy

Research

Li Nie¹  Tianyu Zhao¹  Wenping Luo¹  Hongmei Zhang²  Jing Hu²  Yeming Li²  Xi Tan²  Zhuohui Yang²  Liwen Zheng²  Yuxin Zhang²  Huan Zeng²  Yucan Jiang²  Tong-Chuan He³ 

[1] Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology of Chongqing Medical University, 426 Songshibei Road, 401147, Chongqing, China;Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China;Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology of Chongqing Medical University, 426 Songshibei Road, 401147, Chongqing, China;Department of Pediatric Dentistry, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, China;Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, 60637, Chicago, IL, USA;

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

DOI  :  10.1186/s13287-022-03221-3

 received in 2022-07-20, accepted in 2022-12-12,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundBMP9-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.MethodsIntrabony 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.ResultsBMP9-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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s) 2022

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