Recombinant human bone morphogenetic protein-2 promotes osteogenesis within atelopeptide type I collagen solution by combination with rat cultured marrow cells

Recombinant human bone morphogenetic protein-2 promotes osteogenesis within atelopeptide type I collagen solution by combination with rat cultured marrow cells
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DOI:
10.1002/jbm.1281
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发表时间:
2002-04-01
期刊:
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子:
--
通讯作者:
Sugimura, M
Sugimura, M
中科院分区:
其他
文献类型:
--
作者:
Ikeuchi, M;Dohi, Y;Sugimura, M

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为了开发一种具有稳定成骨能力的骨替代材料,我们在扩散室(DC)中评价了重组人骨形态发生蛋白-2(rhBMP-2)和在端肽I型胶原(AC)溶液中培养的大鼠骨髓间充质干细胞(MSCs)对成骨的联合作用。取新鲜Fischer大鼠骨髓细胞原代培养10 d,获得培养的MSCs。我们制备了三组DC:含有rhBMP-2的AC溶液、含有培养的MSC的AC溶液以及含有rhBMP-2和培养的MSC的AC溶液。将制备的组合溶液注射到DC中,将DC皮下植入同系大鼠背部。在2、4或8周后收获DC,并通过确定组织学和成骨细胞生化标志物来分析成骨能力。AC + rhBMP-2组和MSCs组的DCs膜滤器内外均可见新生骨形成。AC液+rhBMP-2+培养MSCs组碱性磷酸酶活性和骨钙素含量在任何时间点均显著高于AC液+培养MSCs组。这些结果表明,AC水溶液是一种有用的材料,不仅作为载体的rhBMP-2,而且作为细胞锚定的MSC的分化和增殖。因此,本研究表明,使用可注射AC溶液与rhBMP-2和培养的MSC作为骨替代物的骨缺损的临床修复是可行的。(C)John Wiley & Sons,Inc. J Biomed Mater Res 60:61-69,2002.
We evaluated the combination effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and cultured rat bone marrow mesenchymal stem cells (MSCs) in atelopeptide type I collagen (AC) solution on osteogenesis in a diffusion chamber (DC) to develop a bone substitute having consistent osteogenic capability for clinical applications. The cultured MSCs were obtained by 10-day primary culture of fresh bone marrow cells of Fischer rats. We prepared three groups of DCs: AC solution with rhBMP-2, AC solution with cultured MSCs, and AC solution with rhBMP-2 and cultured MSCs. The prepared combined solutions were injected into DCs, which were subcutaneously implanted into the backs of syngeneic rats. DCs were harvested after 2, 4, or 8 weeks and analyzed for bone-forming capability by determining histological and osteoblastic biochemical markers. De novo bone formation was observed both inside and outside of the membrane filter of DCs in the group of AC solution with rhBMP-2 and cultured MSCs. The alkaline phosphatase activity and osteocalcin content in the group of AC solution with rhBMP-2 and cultured MSCs were significantly higher than those in the group of AC solution with cultured MSCs at any time. These findings indicate that AC aqueous solution is a useful material not only as a carrier of rhBMP-2 but also as a cell-anchorage for differentiation and proliferation of MSCs. Therefore, this study suggests that clinical repairs of bone defects are feasible using injectable AC solution with rhBMP-2 and cultured MSCs as a bone substitute. (C) 2002 John Wiley & Sons, Inc. J Biomed Mater Res 60: 61-69, 2002.