VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes.
VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes.
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DOI：
10.1038/s41536-021-00189-1
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发表时间：
2021-11-18
影响因子：
7.2
通讯作者：
Hubbell JA
中科院分区：
文献类型：
--
作者：
White MJV;Briquez PS;White DAV;Hubbell JA
慢性不愈合伤口，通常由糖尿病引起，导致生活质量下降，感染和截肢。这些伤口的治疗选择有限。我们之前利用胎盘生长因子-2 （PlGF-2123-144）的肝素结合结构域，设计了生长因子与伤口环境中暴露的细胞外基质（ECM）结合，而胎盘生长因子-2可以混杂地与ECM蛋白结合。在1型糖尿病（T1D） NOD小鼠模型中，工程生长因子（eGFs）改善了再上皮化和肉芽组织形成。egf联合使用效果更强，血管内皮生长因子- a （VEGF-PlGF-2123-144）、血小板衍生生长因子- bb （PDGF-BB-PlGF-2123-144）和肝素结合表皮生长因子（HB-EGF-PlGF-2123-144）的“三联疗法”既能改善伤口愈合，又能比野生型生长因子在给药部位停留的时间明显更长。此外，我们还发现伤口细胞环境的变化，包括M1巨噬细胞、M2巨噬细胞和效应T细胞的数量的变化，在NOD小鼠模型中最能预测伤口愈合的成功。这些结果表明，VEGF-PlGF-2123-144、PDGF-BB-PlGF-2123-144和HB-EGF-PlGF-2123-144三联疗法可能是治疗糖尿病并发症的慢性不愈合伤口的有效方法。
Chronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123–144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors (eGFs) improved both re-epithelialization and granulation tissue formation. eGFs were even more potent in combination, and the “triple therapy” of vascular endothelial growth factor-A (VEGF-PlGF-2123–144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123–144), and heparin-binding epidermal growth factor (HB-EGF-PlGF-2123–144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound-healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123–144, PDGF-BB-PlGF-2123–144, and HB-EGF-PlGF-2123–144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.
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影响因子：
6.5
作者：
Campbell, Laura;Saville, Charis R.;Murray, Peter J.;Cruickshank, Sheena M.;Hardman, Matthew J.
通讯作者：
Hardman, Matthew J.
影响因子：
--
作者：
Black, E;Vibe-Petersen, J;Gottrup, F
通讯作者：
Gottrup, F
影响因子：
4
作者：
Alonso, L;Fuchs, E
通讯作者：
Fuchs, E
DOI：
10.1111/wrr.12415
发表时间：
2016-03
期刊：
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子：
--
作者：
Bodnar RJ;Satish L;Yates CC;Wells A
通讯作者：
Wells A
影响因子：
15.3
作者：
BROWN, LF;YEO, KT;BERSE, B;YEO, TK;SENGER, DR;DVORAK, HF;VANDEWATER, L
通讯作者：
VANDEWATER, L