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Cxcr6-Based Mesenchymal Stem Cell Gene Therapy Potentiates Skin Regeneration in Murine Diabetic Wounds.
Molecular Therapy ( IF 12.1 ) Pub Date : 2020-02-14 , DOI: 10.1016/j.ymthe.2020.02.014
Neha R Dhoke 1 , Komal Kaushik 1 , Amitava Das 1
Affiliation  

Mesenchymal stem cell (MSC) therapies for wound healing are often compromised due to low recruitment and engraftment of transplanted cells, as well as delayed differentiation into cell lineages for skin regeneration. An increased expression of chemokine ligand CXCL16 in wound bed and its cognate receptor, CXCR6, on murine bone-marrow-derived MSCs suggested a putative therapeutic relevance of exogenous MSC transplantation therapy. Induction of the CXCL16-CXCR6 axis led to activation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinases 1/2 (ERK1/2)-mediated matrix metalloproteinases (MMP)-2 promoter regulation and expression, the migratory signaling pathways in MSC. CXCL16 induction also increased the transdifferentiation of MSCs into endothelial-like cells and keratinocytes. Intravenous transplantation of allogenic stable MSCs with Cxcr6 gene therapy potentiated skin tissue regeneration by increasing recruitment and engraftment as well as neovascularization and re-epithelialization at the wound site in excisional splinting wounds of type I and II diabetic mice. This study suggests that activation of the CXCL16-CXCR6 axis in bioengineered MSCs with Cxcr6 overexpression provides a promising therapeutic approach for the treatment of diabetic wounds.

中文翻译:

基于Cxcr6的间充质干细胞基因治疗增强了小鼠糖尿病伤口的皮肤再生。

由于移植细胞的募集和移入率低,以及延迟分化为皮肤再生的细胞谱系,用于伤口愈合的间充质干细胞(MSC)治疗常常受到损害。趋化因子配体CXCL16在鼠源性骨髓间充质干细胞的创面及其同源受体CXCR6中的表达增加,提示外源性MSC移植治疗具有潜在的治疗意义。CXCL16-CXCR6轴的诱导导致粘着斑激酶(FAK),Src和细胞外信号调节激酶1/2(ERK1 / 2)介导的基质金属蛋白酶(MMP)-2启动子的调控和表达的活化MSC中的信号通路。CXCL16诱导还增加了MSC向内皮样细胞和角质形成细胞的转分化作用。用Cxcr6基因疗法对同种异体稳定MSC进行静脉移植可通过增加I型和II型糖尿病小鼠夹板伤口的募集和植入以及伤口部位的新血管形成和再上皮形成来增强皮肤组织再生。这项研究表明,在生物工程化的MSC中激活CXCL16-CXCR6轴具有Cxcr6过表达,这为治疗糖尿病伤口提供了一种有希望的治疗方法。
更新日期:2020-02-14
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