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富含血小板血浆与脂肪来源干细胞联合通过激活Rho GTPase介导的信号通路促进皮肤伤口愈合。

Platelet-rich plasma in combination with adipose-derived stem cells promotes skin wound healing through activating Rho GTPase-mediated signaling pathway.

作者信息

Zhang Lei, Zhang Baojian, Liao Boyu, Yuan Sha, Liu Yanqun, Liao Zhengyin, Cheng Biao

机构信息

Department of Plastic Surgery, General Hospital of Southern Theater Command, PLA Guangzhou 510010, China.

Institute of Huabo Biopharmaceutical Guangzhou 510010, China.

出版信息

Am J Transl Res. 2019 Jul 15;11(7):4100-4112. eCollection 2019.

PMID:31396321
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6684921/
Abstract

Adipose-derived stem cells (ADSCs) are multipotent stromal cells that provide an abundant source of cells for skin tissue engineering and wound healing. Platelet-rich plasma (PRP) is a concentrate of platelet-rich plasma protein, which contains several different growth factors and other cytokines. In this study, we combined ADSCs with PRP for wound healing. Herein, we found ADSCs in combination with PRP was able to promote wound healing, granulation formation, collagen deposition and re-epithelialization. The mechanism exploration discovered that PRP promoted stress fiber formation in ADSCs, leading to cell migration. Then, we demonstrated that PRP enhanced the expression of Rho GTP family proteins, including Cdc 42, Rac 1 and Rho A. Moreover, it promoted the expression of downstream Rho GTP signaling molecules, including PAK 1, ROCK 2, LIMK 1 and Cofilin. When PRP was used in combination with the Cdc 42 inhibitor ZCL278, the Rho A inhibitor CT04, Rac 1 inhibitor NSC23766, PAK inhibitor FRAX597, or Rock 2 inhibitor Y27632 to treat ADSCs, stress fiber formation was significantly reduced, resulting in decreased cell migration. Our findings may provide a promising approach to promote wound healing.

摘要

脂肪来源干细胞(ADSCs)是多能间充质细胞,为皮肤组织工程和伤口愈合提供了丰富的细胞来源。富血小板血浆(PRP)是富含血小板血浆蛋白的浓缩物,其中含有几种不同的生长因子和其他细胞因子。在本研究中,我们将ADSCs与PRP联合用于伤口愈合。在此,我们发现ADSCs与PRP联合能够促进伤口愈合、肉芽形成、胶原蛋白沉积和再上皮化。机制探索发现,PRP促进了ADSCs中应力纤维的形成,导致细胞迁移。然后,我们证明PRP增强了Rho GTP家族蛋白的表达,包括Cdc 42、Rac 1和Rho A。此外,它促进了下游Rho GTP信号分子的表达,包括PAK 1、ROCK 2、LIMK 1和Cofilin。当PRP与Cdc 42抑制剂ZCL278、Rho A抑制剂CT04、Rac 1抑制剂NSC23766、PAK抑制剂FRAX597或Rock 2抑制剂Y27632联合用于处理ADSCs时,应力纤维的形成显著减少,导致细胞迁移减少。我们的研究结果可能为促进伤口愈合提供一种有前景的方法。

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本文引用的文献

1
Activin B regulates adipose-derived mesenchymal stem cells to promote skin wound healing via activation of the MAPK signaling pathway.激活素B通过激活丝裂原活化蛋白激酶(MAPK)信号通路来调节脂肪来源的间充质干细胞,以促进皮肤伤口愈合。
Int J Biochem Cell Biol. 2017 Jun;87:69-76. doi: 10.1016/j.biocel.2017.04.004. Epub 2017 Apr 8.
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The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery.脂肪来源干细胞(ADSC)在整形和重建手术中的再生作用。
Int Wound J. 2017 Feb;14(1):112-124. doi: 10.1111/iwj.12569. Epub 2016 Feb 1.
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Tissue engineering and ureter regeneration: is it possible?组织工程与输尿管再生:这可行吗?
Int J Artif Organs. 2013 Jun 25;36(6):392-405. doi: 10.5301/ijao.5000130. Epub 2013 May 6.
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Adipose-derived stem cells: fatty potentials for therapy.脂肪干细胞:治疗的脂肪潜能。
Int J Biochem Cell Biol. 2013 Jun;45(6):1083-6. doi: 10.1016/j.biocel.2013.02.013. Epub 2013 Mar 1.
5
Topically delivered adipose derived stem cells show an activated-fibroblast phenotype and enhance granulation tissue formation in skin wounds.局部递送的脂肪来源干细胞呈现激活的成纤维细胞表型,并增强皮肤伤口的肉芽组织形成。
PLoS One. 2013;8(1):e55640. doi: 10.1371/journal.pone.0055640. Epub 2013 Jan 31.
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Platelet-rich plasma.富含血小板血浆
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Platelet-rich plasma: a promising product for treatment of peripheral nerve regeneration after nerve injury.富血小板血浆:一种有前途的治疗周围神经损伤后神经再生的产品。
Int J Neurosci. 2011 Apr;121(4):176-80. doi: 10.3109/00207454.2010.544432. Epub 2011 Jan 19.
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Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair.细胞外基质支架和脂肪来源干细胞在创伤修复过程中的协同血管生成促进作用。
Tissue Eng Part A. 2011 Mar;17(5-6):725-39. doi: 10.1089/ten.TEA.2010.0331. Epub 2010 Dec 18.
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Platelet-rich plasma in muscle healing.富含血小板的血浆在肌肉愈合中的应用。
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Platelet-rich plasma: from basic science to clinical applications.富含血小板的血浆:从基础科学到临床应用。
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