Gohil Shalini V, Adams Douglas J, Maye Peter, Rowe David W, Nair Lakshmi S
Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, Connecticut, 06032; Institute for Regenerative Engineering, The Raymond Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, Connecticut, 06032.
J Biomed Mater Res A. 2014 Dec;102(12):4568-80. doi: 10.1002/jbm.a.35122. Epub 2014 Mar 3.
The aim of the study is use of transgenic fluorescent protein reporter mouse models to understand the cellular processes in recombinant human bone morphogenetic protein-2 (rhBMP-2) mediated bone formation. Bilateral parietal calvarial bone defects in Col3.6Topaz transgenic fluorescent osteoblast reporter mouse were used to understand the bone formation in the presence and absence of rhBMP2 and/or Col3.6Cyan bone marrow derived stromal cells (BMSCs), using collagen-hydroxyapatite matrix (Healos) as a biomaterial. The bone regeneration was not confined to the site of BMP-2 implantation and significant bone formation was observed in the neighboring defect site. Osteogenic cellular activity with overlying alizarin complexone staining was observed in both the defects indicating host cell induced mineralization. However, implantation of BMSCs along with rhBMP-2 demonstrated a donor cell derived bone formation. The presence of rhBMP-2 did not support host cell recruitment in the presence of donor cells. This study demonstrates the potential of multiple fluorescent reporters to understand the cellular processes involved in the bone regeneration process using biomaterials, growth factors, and/or stem cells.
本研究的目的是利用转基因荧光蛋白报告基因小鼠模型，了解重组人骨形态发生蛋白-2（rhBMP-2）介导的骨形成过程中的细胞进程。在Col3.6Topaz转基因荧光成骨细胞报告基因小鼠中制造双侧顶骨颅骨缺损，以了解在有或没有rhBMP2和/或Col3.6青色骨髓来源的基质细胞（BMSC）的情况下的骨形成情况，使用胶原-羟基磷灰石基质（Healos）作为生物材料。骨再生并不局限于BMP-2植入部位，在相邻的缺损部位观察到明显的骨形成。在两个缺损部位均观察到有成骨细胞活性以及茜素络合物染色，表明是宿主细胞诱导的矿化。然而，将BMSC与rhBMP-2一起植入显示有供体细胞来源的骨形成。在有供体细胞存在的情况下，rhBMP-2的存在不支持宿主细胞募集。本研究证明了多种荧光报告基因在利用生物材料、生长因子和/或干细胞了解骨再生过程中所涉及的细胞进程方面的潜力。
