Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats.
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DOI:
10.3390/life12101567
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发表时间:
2022-10-09
期刊:
Life (Basel, Switzerland)
影响因子:
--
通讯作者:
Han Z
Han Z
中科院分区:
其他
文献类型:
--
作者:
Niu Q;Yang Y;Li D;Guo W;Wang C;Xu H;Feng Z;Han Z

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游离组织瓣移植是临床修复组织缺损的经典且重要的方法。然而,缺血再灌注(IR)损伤会影响皮瓣移植的成功率。我们使用游离腹部皮瓣大鼠模型来探讨骨髓间充质干细胞来源的外泌体(BMSCs-exosome)对皮瓣IR损伤的保护作用。通过尾静脉注射外泌体,第7天观察并获得皮瓣。我们观察到BMSCs-外泌体显着减少了皮瓣的坏死病灶。此外,BMSCs-外泌体可以缓解氧化应激并降低炎症因子的水平。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 测定和 Bax、Bcl-2 的蛋白质印迹分析来评估细胞凋亡。同时,BMSCs-外泌体促进了 IR 皮瓣中新血管的形成,VEGFA 表达水平增加以及 CD31 和 PCNA 荧光共染色证实了这一点。此外,BMSCs-外泌体显着增加人脐静脉内皮细胞的增殖和迁移,并促进体外血管生成。 BMSCs-外泌体可能是一种有前途的无细胞治疗候选物,可减少 IR 损伤并促进皮瓣的存活。
Free tissue flap transplantation is a classic and important method for the clinical repair of tissue defects. However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-exosomes) against the IR injury of the skin flap. Exosomes were injected through the tail vein and the flaps were observed and obtained on day 7. We observed that BMSCs-exosomes significantly reduced the necrotic lesions of the skin flap. Furthermore, BMSCs-exosomes relieved oxidative stress and reduced the levels of inflammatory factors. Apoptosis was evaluated via the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and Western blot analysis of Bax, Bcl-2. Simultaneously, BMSCs-exosomes promoted the formation of new blood vessels in the IR flap, as confirmed by the increased expression level of VEGFA and the fluorescence co-staining of CD31 and PCNA. Additionally, BMSCs-exosomes considerably increased proliferation and migration of human umbilical vein endothelial cells and promoted angiogenesis in vitro. BMSCs-exosomes could be a promising cell-free therapeutic candidate to reduce IR injury and promote the survival of skin flaps.
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