Blocking vascular endothelial growth factor with soluble Flt-1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells.
Blocking vascular endothelial growth factor with soluble Flt-1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells.
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DOI：
10.1002/art.24153
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发表时间：
2009-01
影响因子：
--
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Kubo, Seiji;Cooper, Gregory M.;Matsumoto, Tomoyuki;Phillippi, Julie A.;Corsi, Karin A.;Usas, Arvydas;Li, Guangheng;Fu, Freddie H.;Huard, Johnny
目的：探讨血管内皮生长因子(VEGF)的刺激作用及其拮抗剂sFlt1对骨骼肌源性干细胞(MDSCs)诱导成软骨的影响。采用颗粒培养系统检测血管内皮生长因子对小鼠骨髓间充质干细胞体外成软骨能力的直接影响，并进行实时定量聚合酶链式反应和组织学分析。接下来，通过将基因工程的MDSCs植入大鼠的骨软骨缺损处，测试了血管内皮生长因子对滑膜关节内软骨形成的影响。在该模型中，用逆转录病毒载体转导表达BMP4的MDSCs与转导表达VEGF或sFlt1(一种血管内皮生长因子拮抗剂)的MDSCs共植入，以提供一个关于VEGF功能的得失的实验设计。用组织学评分比较治疗组之间的软骨形成情况。实时荧光定量聚合酶链式反应显示，经BMP4和转化生长因子-β3诱导分化的MDSCs中，sFlt1促进了成软骨基因的表达。体内关节软骨修复实验表明，转导sFlt1的MDSCs引起了膝关节关节炎的改变，sFlt1促进了mdsc介导的关节软骨修复。SFlt1基因治疗可提高BMP4和转化生长因子β3诱导的MDSCs的成软骨基因表达，并通过阻止修复关节软骨的血管化和骨侵袭而提高修复关节软骨的持久性。
To investigate the effect of VEGF stimulation and the effect of blocking VEGF with its antagonist, sFlt1, on chondrogenesis using skeletal muscle-derived stem cells (MDSCs). The direct effect of VEGF on the in vitro chondrogenic ability of mouse MDSCs was tested using a pellet culture system followed by quantitative real time PCR and histological analyses. Next, the effect of VEGF on chondrogenesis within the synovial joint was tested using genetically engineered MDSCs implanted into the rat osteochondral defect. In this model, MDSCs, transduced with a retroviral vector to express BMP4, were co-implanted with MDSCs transduced to express either VEGF or sFlt1 (a VEGF antagonist) to provide a gain- and loss-of VEGF function experimental design. Histological scoring was used to compare cartilage formation among the treatment groups. Hyaline-like cartilage matrix production was observed in both VEGF-treated and VEGF-blocked (sFlt1-treated) pellet cultures, but real-time PCR revealed that sFlt1 treatment improved the expression of chondrogenic genes in MDSCs that were stimulated to undergo chondrogenic differentiation with BMP4 and TGF-β3. In vivo testing of articular cartilage repair showed that VEGF-transduced MDSCs caused an arthritic change in the knee joint, and sFlt1 improved the MDSC-mediated repair of articular cartilage, compared to BMP4 alone. sFlt1 gene therapy improved BMP4- and TGF-β3-induced chondrogenic gene expression of MDSCs in vitro, and improved the persistence of repaired articular cartilage by preventing vascularization and bone invasion into the repaired articular cartilage.
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DOI：
10.1083/jcb.200108150
发表时间：
2002-05-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Qu-Petersen Z;Deasy B;Jankowski R;Ikezawa M;Cummins J;Pruchnic R;Mytinger J;Cao B;Gates C;Wernig A;Huard J
通讯作者：
Huard J
影响因子：
4.8
作者：
Jadlowiec, J;Koch, H;Sfeir, C
通讯作者：
Sfeir, C
影响因子：
3.3
作者：
Deasy, BM;Gharaibeh, BM;Huard, J
通讯作者：
Huard, J
影响因子：
5.2
作者：
Koga, Hideyuki;Muneta, Takeshi;Sekiya, Ichiro
通讯作者：
Sekiya, Ichiro
影响因子：
4.4
作者：
De Bandt, M;Ben Mahdi, MH;Pasquier, C
通讯作者：
Pasquier, C