A study of the role of Nell-1 gene modified goat bone marrow stromal cells in promoting new bone formation
A study of the role of Nell-1 gene modified goat bone marrow stromal cells in promoting new bone formation
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DOI：
10.1038/sj.mt.6300270
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发表时间：
2007-10-01
影响因子：
12.4
通讯作者：
Zhang, Xinli
中科院分区：
文献类型：
--
作者：
Aghaloo, Tara;Jiang, Xinquan;Zhang, Xinli
Nell-1是最近发现的一种分泌蛋白，在各种啮齿动物模型中具有促进成骨颅骨细胞分化和矿化，诱导颅骨骨过度生长和再生的能力。然而，在大型动物细胞中，Nell-1骨诱导能力的程度尚不清楚。本研究的目的是评估在体外和体内将编码Nell-1 （AdNell-1）基因的腺病毒转移到原代成年山羊骨髓基质细胞（BMSCs）的可行性，并将其与骨形态发生蛋白-2 （BMP-2）产生的成骨效果进行比较，BMP-2是一种成熟的骨诱导分子，目前用于区域基因治疗。adnell -1转导的骨髓间充质干细胞在体外2周内表达Nell-1蛋白并发生成骨细胞分化，与AdBMP-2相当。肌内注射裸鼠后，AdNell-1和adbmp -2转导的骨髓间充质干细胞显示新骨形成，而未转导或adlacz转导的骨髓间充质干细胞主要表现为纤维化组织增殖。在第4周，BMP-2诱导的骨量明显增大，骨缘成熟，中央腔主要充满脂肪性骨髓组织。Nell-1样品的骨量明显减少，但在组织学上与新形成的小梁骨混合软骨样骨区相似，经X型胶原（ColX）免疫组化证实。这种组织形态学与BMP-2诱导的骨量的明显差异表明，Nell-1在骨组织工程和再生中具有潜在的临床作用/优势。
Nell-1 is a recently discovered secreted protein with the capacity to promote osteoblastic calvarial cell differentiation and mineralization and induce calvarial bone overgrowth and regeneration in various rodent models. However, the extent of Nell-1 osteoinductivity in large animal cells remains unknown. The objective of the study was to evaluate the feasibility of adenoviral encoding Nell-1 (AdNell-1) gene transfer into primary adult goat bone marrow stromal cells (BMSCs) in vitro and in vivo and to compare the osteoinductive effects with those produced by bone morphogenetic protein-2 (BMP-2), a well established osteoinductive molecule currently utilized for regional gene therapy. AdNell-1-transduced BMSCs expressed Nell-1 protein and underwent osteoblastic differentiation within 2 weeks in vitro, which is comparable to AdBMP-2. After intramuscular injection of nude mice, the AdNell-1- and AdBMP-2-transduced BMSCs revealed new bone formation, while untransduced or AdLacZ-transduced BMSCs showed mainly fibrotic tissue proliferation. At 4 weeks, BMP-2 induced significantly larger bone mass with a mature bone margin and central cavity filled with primarily fatty marrow tissue. Nell-1 samples had significantly less bone mass but were histologically similar to newly formed trabecular bone mixed with chondroid bone-like areas verified by type X collagen (ColX) immunohistochemistry. This distinct difference in histomorphology from the bone mass induced by BMP-2 suggests that there is a potential clinical role/advantage for Nell-1 in skeletal tissue engineering and regeneration.