The Multiplicity of Infection-Dependent Effects of Recombinant Adenovirus Carrying HGF Gene on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.
The Multiplicity of Infection-Dependent Effects of Recombinant Adenovirus Carrying HGF Gene on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.
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携带HGF基因的重组腺病毒对人骨髓间充质干细胞增殖和成骨分化的多重感染依赖性影响
DOI：
10.3390/ijms19030734
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发表时间：
2018-03-05
影响因子：
5.6
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Wen Q;Zhang S;Du X;Wang R;Li Y;Liu H;Hu S;Zhou C;Zhou X;Ma L
股骨头缺血性坏死（ANFH）缺乏有效的治疗方法，一直困扰着世界医学界。骨髓间充质干细胞（BMSCs）过继细胞治疗联合髓芯减压术是一种很有前途的治疗方法，其高度依赖于BMSCs的细胞活性。肝细胞生长因子（HGF）是骨髓间充质干细胞的一种存活因子，但其潜在机制尚未完全阐明。本研究系统研究了携带HGF基因的重组腺病毒（rAd-HGF）感染复数（MOIs）对人骨髓基质细胞（BMSC）增殖和成骨分化的影响。rAd-HGF的感染产生分泌型HGF，并以MOI依赖的方式促进hBMSC增殖，同时骨生成也得到加强，如通过增强钙结节形成所示，在MOI = 250时达到最强的效果。阻断c-MET或其下游信号通路、WNT、ERK 1/2和PI 3 K/AKT的活性导致不同的结果。具体而言，阻断WNT通路显著促进成骨分化，当与rAd-HGF联合应用时，也显示出累加效应。我们的数据表明，优化MOI的rAd-HGF的促成骨作用，而抑制WNT通路或激活PI 3 K/AKT通路可能作为候选的佐剂模式，促进成骨分化的rAd-HGF修饰的hBMSC治疗ANFH。
Absence of effective therapeutic methods for avascular necrosis of femoral head (ANFH) is still perplexing the world’s medical community. Bone marrow mesenchymal stem cells (BMSCs) adoptive cell therapy combined with core decompression is a promising modality, which is highly dependent on the cellular activities of BMSCs. Hepatocyte growth factor (HGF) is a survival factor for BMSCs, yet the underlying mechanism is not fully elucidated. In this study, the effects of multiplicity of infections (MOIs) of recombinant adenovirus carrying HGF gene (rAd-HGF) on human BMSC proliferation and osteogenic differentiation were systemically examined. Infection of rAd-HGF produced secretory HGF and promoted hBMSC proliferation in a MOI-dependent manner, while the osteogenesis was also strengthened as indicated by enhanced calcium nodule formation with the strongest effects achieved at MOI = 250. Blocking the activities of c-MET or its downstream signaling pathways, WNT, ERK1/2, and PI3K/AKT led to differential consequents. Specifically, blockage of the WNT pathway significantly promoted osteogenic differentiation, which also showed additive effects when combined application with rAd-HGF. Our data demonstrated the pro-osteogenic effects of optimized MOIs of rAd-HGF, while inhibition of WNT pathway or activation of PI3K/AKT pathway may act as candidate adjuvant modalities for promoting osteogenic differentiation in rAd-HGF-modified hBMSC treatment on ANFH.
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DOI：
10.1016/j.bbrc.2014.01.084
发表时间：
2014-02-28
影响因子：
3.1
作者：
Eom, Young Woo;Oh, Ji-Eun;Shim, Kwang Yong
通讯作者：
Shim, Kwang Yong
影响因子：
4.8
作者：
Gaur, T;Lengner, CJ;Lian, JB
通讯作者：
Lian, JB
影响因子：
7.7
作者：
Guo, Yinghua;He, Jianguo;Liang, Lirong
通讯作者：
Liang, Lirong
影响因子：
3.5
作者：
Tabatabaee, Reza Mostafavi;Saberi, Sadegh;Farzan, Mahmoud
通讯作者：
Farzan, Mahmoud
肝细胞生长因子浓度的变化促进了间充质干细胞介导的成骨重生。
影响因子：
5.3
作者：
Wen Q;Zhou L;Zhou C;Zhou M;Luo W;Ma L
通讯作者：
Ma L