Su Zhong-Ping, Tian Lei, Shang Hong-Tao, Yang Yong, Lu Jin-Biao, Kang Yong-Jie, He Li-Sheng, Zhao Jin-Long
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Front Surg. 2022 Feb 9;8:786351. doi: 10.3389/fsurg.2021.786351. eCollection 2021.
The present study aims to increase the concentration of genetically modified bone marrow mesenchymal stem cells (BMSCs) in the distraction osteogenesis (DO) interstitial space and induce the conversion of BMSCs to osteoblasts to improve the osteogenic efficiency in DO and shorten the treatment period.
Bone morphogenetic protein 1 (BMP-1) and green fluorescent protein (GFP) gene-modified cell sheets of BMSCs were constructed by tissue engineering. Thirty-six New Zealand white rabbits were randomly divided into three groups: group A (the blank control group), group B (the GFP group) with the injection of GFP gene-modified BMSC sheets into the DO gap, and group C (the BMP-1 group) with the injection of BMP-1 gene-modified BMSC sheets into the DO gap. Rabbits in all three groups were distracted for 5 days at a distraction rate of 2.0 mm/d, once/day. After distraction, the above-mentioned cell sheet suspension was injected into the distraction gap to observe osteogenesis, which was observed by gross specimen observation, micro-computed tomography (Micro-CT) scanning, and histomorphology.
The gross specimen observation showed that all animals had smooth and continuous bone cortex in the distraction region with relatively high hardness. The osteogenesis quality or hardness was ranked from the highest to the lowest, as Group C > Group B > Group A. Micro-CT and histomorphological observation revealed that group C had better maturation and bone volume of the new bone in the DO region at weeks 3 and 6 than groups B and A.
BMP-1 gene-modified BMSC sheets could effectively promote the formation of new bone during rapid DO in the mandible, compensating for the poor osteogenesis caused by rapid distraction and providing a new approach to shorten the DO treatment period in clinical practice.
本研究旨在提高转基因骨髓间充质干细胞(BMSCs)在牵张成骨(DO)间隙中的浓度,并诱导BMSCs向成骨细胞转化,以提高DO的成骨效率并缩短治疗周期。
通过组织工程构建骨形态发生蛋白1(BMP-1)和绿色荧光蛋白(GFP)基因修饰的BMSCs细胞片。36只新西兰白兔随机分为三组:A组(空白对照组)、B组(GFP组),将GFP基因修饰的BMSCs细胞片注入DO间隙,C组(BMP-1组),将BMP-1基因修饰的BMSCs细胞片注入DO间隙。三组兔子均以2.0 mm/d的牵张速率牵张5天,每天1次。牵张后,将上述细胞片悬液注入牵张间隙观察成骨情况,通过大体标本观察、显微计算机断层扫描(Micro-CT)和组织形态学进行观察。
大体标本观察显示,所有动物牵张区域的骨皮质光滑连续,硬度较高。成骨质量或硬度从高到低依次为:C组>B组>A组。Micro-CT和组织形态学观察显示,在第3周和第6周时,C组在DO区域的新骨成熟度和骨体积优于B组和A组。
BMP-1基因修饰的BMSCs细胞片可有效促进下颌骨快速DO过程中新生骨的形成,弥补快速牵张导致的成骨不良,为临床缩短DO治疗周期提供了新途径。