Lysophosphatidic acid enhances stromal cell-directed angiogenesis.
Lysophosphatidic acid enhances stromal cell-directed angiogenesis.
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DOI：
10.1371/journal.pone.0082134
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Leach JK
中科院分区：
文献类型：
--
作者：
Binder BY;Sondergaard CS;Nolta JA;Leach JK
缺血性疾病如外周血管疾病（PVD）影响超过15%的一般人群，并且在严重的情况下导致溃疡、坏死和肢体丧失。虽然生长因子的治疗性递送以促进血管生成已被广泛研究，但大规模实施受到有效递送昂贵重组蛋白的策略的限制。多能脂肪源性基质细胞（ASC）和其他组织隔室的祖细胞分泌的血管生成分子的生物活性浓度，使基于细胞的策略，原位交付的血管生成细胞因子的一个令人兴奋的替代重组蛋白的使用。在这里，我们表明，磷脂溶血磷脂酸（LPA）协同改善缺血ASC的促血管生成作用。我们发现，LPA上调血管生成生长因子的生产ASC下的二维和三维体外模型的血清剥夺和缺氧（SD/H），这些因素显着增强内皮细胞迁移。与单独的LPA或ASC相比，LPA和ASC在纤维蛋白凝胶中的同时递送显著改善了鼠严重后肢缺血模型中的血管形成，从而显示出该方法的转化潜力。此外，这些结果是使用廉价的脂质分子实现的，其比正在研究用于类似用途的重组生长因子便宜几个数量级。我们的研究结果证明了一种新的策略，用于增强基于细胞的治疗性血管生成的策略，在治疗缺血性疾病方面具有重要的应用。
Ischemic diseases such as peripheral vascular disease (PVD) affect more than 15% of the general population and in severe cases result in ulcers, necrosis, and limb loss. While the therapeutic delivery of growth factors to promote angiogenesis has been widely investigated, large-scale implementation is limited by strategies to effectively deliver costly recombinant proteins. Multipotent adipose-derived stromal cells (ASC) and progenitor cells from other tissue compartments secrete bioactive concentrations of angiogenic molecules, making cell-based strategies for in situ delivery of angiogenic cytokines an exciting alternative to the use of recombinant proteins. Here, we show that the phospholipid lysophosphatidic acid (LPA) synergistically improves the proangiogenic effects of ASC in ischemia. We found that LPA upregulates angiogenic growth factor production by ASC under two- and three-dimensional in vitro models of serum deprivation and hypoxia (SD/H), and that these factors significantly enhance endothelial cell migration. The concurrent delivery of LPA and ASC in fibrin gels significantly improves vascularization in a murine critical hindlimb ischemia model compared to LPA or ASC alone, thus exhibiting the translational potential of this method. Furthermore, these results are achieved using an inexpensive lipid molecule, which is orders-of-magnitude less costly than recombinant growth factors that are under investigation for similar use. Our results demonstrate a novel strategy for enhancing cell-based strategies for therapeutic angiogenesis, with significant applications for treating ischemic diseases.
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影响因子：
120.1
作者：
Cao, Yihai
通讯作者：
Cao, Yihai
影响因子：
5.2
作者：
Chen, Jinghai;Baydoun, Anwar R.;Chen, Xi
通讯作者：
Chen, Xi
影响因子：
4
作者：
He, Jiawei;Genetos, Damian C.;Leach, J. Kent
通讯作者：
Leach, J. Kent
DOI：
10.1073/pnas.1221309110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Awojoodu, Anthony O.;Ogle, Molly E.;Botchwey, Edward
通讯作者：
Botchwey, Edward
影响因子：
4.1
作者：
He, Jiawei;Genetos, Damian C.;Leach, J. Kent
通讯作者：
Leach, J. Kent