Omental grafting: a cell-based therapy for blood vessel repair.
Omental grafting: a cell-based therapy for blood vessel repair.
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DOI：
10.1002/term.528
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发表时间：
2013-06
影响因子：
3.3
通讯作者：
Bader, David M.
中科院分区：
文献类型：
--
作者：
Shelton, Elaine L.;Poole, Stanley D.;Reese, Jeff;Bader, David M.
临床医生定期移植大网膜蒂来修复各种受损组织，但这种有效手术的基本机制尚不清楚。尚未解决的一种可能性是大网膜直接为受损组织提供再生细胞的能力。我们假设，如果可以动员网膜祖细胞融入受损组织，那么这种疗法的功效将大大扩大。将标记的网膜移植物移植到小鼠颈动脉损伤模型中。选定的移植物在移植前用胸腺素β4 进行处理，以研究化学增强对愈合的影响。我们发现用胸腺肽β4处理移植物可诱导祖细胞完全融入受损血管壁并分化为血管平滑肌。肌动描记研究确定，接受胸腺素β4刺激移植物的动脉在功能上与未受伤的对照动脉没有区别。同时进行的体外分析表明，胸腺素β4 通过 AKT 信号传导促进细胞的增殖、迁移和转分化。这项研究首次证明大网膜可以提供用于修复的祖细胞，从而揭示了一种新颖的、天然存在的血管平滑肌来源，可用于基于细胞的疗法。此外，我们的数据显示该系统可以通过诱导因素进行优化，突显出比当前临床应用更强大的治疗潜力。这是一个范式设定概念，为使用化学遗传学来增强众多领域的治疗效果奠定了基础。
Clinicians regularly transplant omental pedicles to repair a wide variety of injured tissues but the basic mechanism underlying this efficacious procedure is not understood. One possibility that has not been addressed is the ability of omentum to directly contribute regenerative cells to injured tissues. We hypothesized that if omental progenitor cells could be mobilized to incorporate into damaged tissue, the power of this therapy would be greatly expanded. Labeled omental grafts were transplanted into a murine carotid artery injury model. Selected grafts were treated with Thymosinβ4 prior to transplantation to investigate the effects of chemical potentiation on healing. We found treatment of grafts with Thymosinβ4 induced progenitor cells to fully integrate into the wall of injured vessels and differentiate into vascular smooth muscle. Myographic studies determined that arteries receiving Thymosinβ4-stimulated grafts were functionally indistinguishable from uninjured controls. Concurrent in vitro analyzes showed that Thymosinβ4 promoted proliferation, migration, and trans-differentiation of cells via AKT signaling. This study is the first to demonstrate that omentum can provide progenitor cells for repair, thus revealing a novel and naturally occurring source of vascular smooth muscle for use in cell-based therapies. Furthermore, our data show this system can be optimized with inducing factors, highlighting a more powerful therapeutic potential than that of its current clinical application. This is a paradigm-setting concept that lays the foundation for the use of chemical genetics to enhance therapeutic outcomes in a myriad of fields.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
DOI：
10.1161/atvbaha.109.198895
发表时间：
2010-06-01
影响因子：
8.7
作者：
Kumar, Arun H. S.;Caplice, Noel M.
通讯作者：
Caplice, Noel M.
影响因子：
4.6
作者：
Ishikawa, M;Fjii, M;Tashiro, S
通讯作者：
Tashiro, S
影响因子：
4.8
作者：
Philp, D;Huff, T;Kleinman, HK
通讯作者：
Kleinman, HK
影响因子：
3.6
作者：
Reese, Jeff;Waleh, Nahid;Clyman, Ronald I.
通讯作者：
Clyman, Ronald I.