Vascular endothelial growth factor (VEGF) as a key therapeutic trophic factor in bone marrow mesenchymal stem cell-mediated cardiac repair.
Vascular endothelial growth factor (VEGF) as a key therapeutic trophic factor in bone marrow mesenchymal stem cell-mediated cardiac repair.
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DOI：
10.1016/j.bbrc.2009.10.058
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发表时间：
2009-12-18
影响因子：
3.1
通讯作者：
Lee, Techung
中科院分区：
文献类型：
--
作者：
Zisa, David;Shabbir, Arsalan;Suzuki, Gen;Lee, Techung
我们最近证明了一种新的有效的治疗方案，用于治疗仓鼠心力衰竭的基础上注射骨髓间充质干细胞（MSC）或MSC条件培养基到骨骼肌。这项工作突出了一个重要的心脏修复机制，它由来自注射的MSC和局部肌肉组织的无数营养因子介导，可以用于非侵入性干细胞治疗。虽然这种治疗方案提供了基于MSC的心脏修复是由独立于MSC分化或干性的营养作用介导的最终证据，但MSC治疗后负责心脏再生的营养因子在很大程度上仍不确定。为此，我们利用了人类和猪MSC在营养因子表达方面表现出物种相关差异的发现。我们证明，与猪MSC相比，人MSC在条件培养基中表达和分泌的血管内皮生长因子（VEGF）少5倍（分别为40 ± 5和225 ± 17 pg/ml VEGF）。VEGF输出的这种缺陷与人MSC条件培养基的心脏治疗功效受损相关。然而，VEGF在人MSC中的过表达完全恢复了条件培养基的治疗效力。这一发现表明VEGF是MSC介导的心肌再生中的关键治疗营养因子，并证明了使用基于营养因子的无细胞策略进行人MSC治疗的可行性，这可以消除潜在干细胞转化的担忧。
We recently demonstrated a novel effective therapeutic regimen for treating hamster heart failure based on injection of bone marrow mesenchymal stem cells (MSCs) or MSC-conditioned medium into the skeletal muscle. The work highlights an important cardiac repair mechanism mediated by the myriad of trophic factors derived from the injected MSCs and local musculature that can be explored for non-invasive stem cell therapy. While this therapeutic regimen provides the ultimate proof that MSC-based cardiac repair is mediated by the trophic actions independent of MSC differentiation or stemness, the trophic factors responsible for cardiac regeneration after MSC therapy remain largely undefined. Toward this aim, we took advantage of the finding that human and porcine MSCs exhibit species-related differences in expression of trophic factors. We demonstrate that human MSCs when compared to porcine MSCs express and secrete 5-fold less vascular endothelial growth factor (VEGF) in conditioned medium (40 ± 5 and 225 ± 17 pg/ml VEGF, respectively). This deficit in VEGF output was associated with compromised cardiac therapeutic efficacy of human MSC-conditioned medium. Overexpression of VEGF in human MSCs however completely restored the therapeutic potency of the conditioned medium. This finding indicates VEGF as a key therapeutic trophic factor in MSC-mediated myocardial regeneration, and demonstrates the feasibility of human MSC therapy using trophic factor-based cell-free strategies, which can eliminate the concern of potential stem cell transformation.
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影响因子：
4.3
作者：
Missihoun, Comlan;Zisa, David;Shabbir, Arsalan;Lin, Huey;Lee, Techung
通讯作者：
Lee, Techung
影响因子：
5.2
作者：
Oswald, J;Boxberger, S;Werner, C
通讯作者：
Werner, C
影响因子：
37.8
作者：
Iwaguro, H;Yamaguchi, J;Asahara, T
通讯作者：
Asahara, T
影响因子：
11.4
作者：
Asahara, T;Takahashi, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
168.9
作者：
LeBlanc, Katarina;Frassoni, Francesco;Ringden, Olle
通讯作者：
Ringden, Olle