THE COMBINED MECHANISM OF BONE MORPHOGENETIC PROTEIN- AND CALCIUM PHOSPHATE-INDUCED SKELETAL TISSUE FORMATION BY HUMAN PERIOSTEUM DERIVED CELLS
THE COMBINED MECHANISM OF BONE MORPHOGENETIC PROTEIN- AND CALCIUM PHOSPHATE-INDUCED SKELETAL TISSUE FORMATION BY HUMAN PERIOSTEUM DERIVED CELLS
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DOI：
10.22203/ecm.v031a02
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Luyten, F. P.
中科院分区：
文献类型：
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作者：
Bolander, J.;Ji, W.;Luyten, F. P.
当将成骨祖细胞如人骨膜衍生细胞（hPDC）与骨传导性生物材料如磷酸钙（CaP）支架组合时，可以实现体内骨形成。这一过程依赖于骨形态发生蛋白（BMP）信号的早期激活。然而，骨形成过程是缓慢的，并且通常仅形成有限量的骨和骨髓。因此，我们假设通过在这些细胞和CaP构建体中加入更多生理水平的有效BMP配体，可以获得稳健的临床相关结果。为此，hPDCs在体外2D刺激下对BMP配体的反应性进行了表征。BMP-2、BMP-4、BMP-6和BMP-9强烈诱导骨软骨形成分化。随后，将这些配体包被到临床批准的CaP-支架BioOss（R）和CopiOs（R）上，然后接种hPDC。研究了蛋白裂解物和条件培养基对BMP信号通路的激活。在体内植入后，在BMP-2和BMP-6涂覆的支架中发现最丰富的骨形成。植入的细胞积极地促进了新骨的形成。计算分析显示，BMP-配体的类型以及CaP-支架影响骨骼组织的形成，以定性和定量的方式观察。此外，体外机制似乎可以预测体内结果。这项研究提供了进一步的证据，BMP技术的潜力，在临床相关的细胞为基础的结构，骨再生策略的发展。
When combining osteogenic progenitor cells such as human periosteum derived cells (hPDCs) with osteoconductive biomaterials like calcium phosphate (CaP)-scaffolds, in vivo bone formation can be achieved. This process is dependent on the early activation of Bone morphogenetic protein (BMP)-signalling. However, the bone forming process is slow and routinely only a limited amount of bone and bone marrow is formed. Therefore, we hypothesised that a robust clinically relevant outcome could be achieved by adding more physiological levels of potent BMP-ligands to these cell-and CaP-based constructs.For this, hPDCs were characterised for their responsiveness to BMP-ligands upon in vitro 2D stimulation. BMP-2, -4, -6 and -9 robustly induced osteochondrogenic differentiation. Subsequently, these ligands were coated onto clinically approved CaP-scaffolds, BioOss (R) and CopiOs (R), followed by hPDC-seeding. Protein lysates and conditioned media were investigated for activation of BMP signalling pathways. Upon in vivo implantation, the most abundant bone formation was found in BMP-2 and BMP-6-coated scaffolds. Implanted cells actively contributed to the newly formed bone. Remnants of cartilage could be observed in BMP-coated CopiOs (R)-constructs.Computational analysis displayed that the type of BMP-ligand as well as the CaP-scaffold affects skeletal tissue formation, observed in a qualitative as well as quantitative manner. Furthermore, the in vitro mechanism appears to predict the in vivo outcome. This study presents further evidence for the potential of BMP-technology in the development of clinically relevant cell-based constructs for bone regenerative strategies.