Bone marrow mesenchymal stromal cells stimulate skeletal myoblast proliferation through the paracrine release of VEGF.
Bone marrow mesenchymal stromal cells stimulate skeletal myoblast proliferation through the paracrine release of VEGF.
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DOI：
10.1371/journal.pone.0037512
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Formigli L
中科院分区：
文献类型：
--
作者：
Sassoli C;Pini A;Chellini F;Mazzanti B;Nistri S;Nosi D;Saccardi R;Quercioli F;Zecchi-Orlandini S;Formigli L
间充质基质细胞(MSCs)是再生医学领域的主要候选细胞。这些细胞也被成功地用于改善骨骼肌的修复/再生；然而，其有益效果的机制仍有待阐明。在此基础上，本研究在共培养体系中评价了骨髓间充质干细胞对C2C12成肌细胞行为的影响，并从细胞和分子水平分析了两种细胞之间的相互作用。通过时间推移显微镜、细胞周期蛋白A的表达和EDU掺入实验，我们发现共培养的成肌细胞的增殖显著增强。此外，与单独培养相比，免疫磁性分离的MSCs共培养后的成肌细胞表达更高的Notch-1的mRNA和蛋白水平，Notch-1是成肌细胞激活和增殖的关键决定因素。在共培养过程中，Notch-1靶基因Hes-1的胞内结构域和核定位也增加。有趣的是，成肌细胞的反应主要依赖于MSCs对血管内皮生长因子(VEGF)的旁分泌。事实上，在C2C12细胞中加入MSC衍生的条件培养液(CM)产生了与在共培养中观察到的结果相似的结果，并增加了VEGFR的磷酸化和表达水平。用选择性药物VEGFR抑制剂KRN633处理后，受体活性显著减弱，同时抑制MSC-CM对C2C12细胞生长和Notch-1信号转导的影响。综上所述，本研究为MSCs在刺激成肌细胞增殖中的作用提供了新的证据，并提示这两种细胞之间的功能相互作用可能被用于开发新的、更有效的基于细胞的骨骼肌修复策略。
Mesenchymal stromal cells (MSCs) are the leading cell candidates in the field of regenerative medicine. These cells have also been successfully used to improve skeletal muscle repair/regeneration; however, the mechanisms responsible for their beneficial effects remain to be clarified. On this basis, in the present study, we evaluated in a co-culture system, the ability of bone-marrow MSCs to influence C2C12 myoblast behavior and analyzed the cross-talk between the two cell types at the cellular and molecular level. We found that myoblast proliferation was greatly enhanced in the co-culture as judged by time lapse videomicroscopy, cyclin A expression and EdU incorporation. Moreover, myoblasts immunomagnetically separated from MSCs after co-culture expressed higher mRNA and protein levels of Notch-1, a key determinant of myoblast activation and proliferation, as compared with the single culture. Notch-1 intracellular domain and nuclear localization of Hes-1, a Notch-1 target gene, were also increased in the co-culture. Interestingly, the myoblastic response was mainly dependent on the paracrine release of vascular endothelial growth factor (VEGF) by MSCs. Indeed, the addition of MSC-derived conditioned medium (CM) to C2C12 cells yielded similar results as those observed in the co-culture and increased the phosphorylation and expression levels of VEGFR. The treatment with the selective pharmacological VEGFR inhibitor, KRN633, resulted in a marked attenuation of the receptor activation and concomitantly inhibited the effects of MSC-CM on C2C12 cell growth and Notch-1 signaling. In conclusion, this study provides novel evidence for a role of MSCs in stimulating myoblast cell proliferation and suggests that the functional interaction between the two cell types may be exploited for the development of new and more efficient cell-based skeletal muscle repair strategies.
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影响因子：
3.7
作者：
Gang, Eun Ji;Darabi, Radbod;Perlingeiro, Rita C. R.
通讯作者：
Perlingeiro, Rita C. R.
血管细胞对成肌干细胞行为的调控 卫星细胞、内皮周围细胞和内皮细胞的 "三人行"
影响因子：
4.3
作者：
Abou-Khalil, Rana;Mounier, Remi;Chazaud, Benedicte
通讯作者：
Chazaud, Benedicte
DOI：
10.1152/ajpheart.01277.2005
发表时间：
2006-09-01
影响因子：
4.8
作者：
Gonzalez-Pacheco, Francisco R.;Deudero, Juan J. P.;Caramelo, Carlos
通讯作者：
Caramelo, Carlos
DOI：
10.1016/j.bbrc.2007.01.045
发表时间：
2007-03-16
影响因子：
3.1
作者：
Iso, Yoshitaka;Spees, Jeffrey L.;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.
影响因子：
64.8
作者：
PARTRIDGE, TA;MORGAN, JE;KUNKEL, LM
通讯作者：
KUNKEL, LM