All-trans retinoic acid improves the viability of ischemic skin flaps in diabetic rat models

Weng, Zhenjun; Wang, Chunyang; Zhang, Cheng; Xu, Jia; Chai, Yimin; Jia, Yuechen; Han, Pei; Wen, Gen

doi:10.1016/j.diabres.2018.06.019

Cited by 9 publications

(4 citation statements)

References 34 publications

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“…However, the survival rate of skin flaps treated by HT-ASC-EVs (approximately 70%) was comparable with that treated by ASCs and higher than that treated by ASC culture medium 11,20 . To compare with other techniques, the survival rate of flaps treated by HT-ASC-EVs were also higher than that treated by all-trans retinoic acid (approximately 40%), hyperbaric oxygen (approximately 60%), and aminoguanidine (approximately 60%) 21–23 …”

Section: Discussionmentioning

confidence: 93%

“…11,20 To compare with other techniques, the survival rate of flaps treated by HT-ASC-EVs were also higher than that treated by all-trans retinoic acid (approximately 40%), hyperbaric oxygen (approximately 60%), and aminoguanidine (approximately 60%). [21][22][23] Extracellular vesicles have several advantages such as low immunogenicity, nontumorigenicity, and nanoscale particle size that does not cause microvascular embolism. 24 Furthermore, bilayer phospholipid membrane of EVs protects the proteins and genetic materials from enzymatic degradation in the microenvironment of damaged tissue.…”

Section: Discussionmentioning

confidence: 99%

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Extracellular Vesicles Isolated From Hypoxia-Preconditioned Adipose-Derived Stem Cells Promote Hypoxia-Inducible Factor 1α–Mediated Neovascularization of Random Skin Flap in Rats

Wang

et al. 2022

Ann Plast Surg

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Background: Random flaps are widely used for wound repair. However, flap necrosis is a serious complication leading to the failure of operation. Our previous study demonstrated a great proangiogenic potential of hypoxia-treated adipose-derived stem cells-extracellular vesicles (HT-ASC-EVs). Thus, we aim to evaluate the effect of HT-ASC-EVs in the survival and angiogenesis of random skin flap in rats. Methods: Adipose-derived stem cells-extracellular vesicles were respectively isolated from adipose-derived stem cell culture medium of 3 donors via ultracentrifugation. The expression of hypoxia-inducible factor 1α (HIF-1α) and proangiogenic potential of HT-ASC-EVs and ASC-EVs were compared by co-culturing with human umbilical vein endothelial cells. Forty male Sprague-Dawley rats were randomly divided into 3 group (n = 10/group). A 9 Â 3-cm random skin flap was separated from the underlying fascia with both sacral arteries sectioned on each rat. The survival and angiogenesis of flaps treated by ASC-EVs or HT-ASC-EVs were also compared. Laser Doppler flowmetry and immunohistochemistry were used to evaluate skin perfusion and angiogenesis of skin flaps on postoperative day 7. Results: Hypoxia-treated adipose-derived stem cells-extracellular vesicles further improve the proliferation, migration, tube formation with upregulated HIF-1α, and VEGF expression of human umbilical vein endothelial cells in vitro, compared with ASC-EVs. In vivo, postoperatively injecting HT-ASC-EVs suppressed necrosis rate (29.1 ± 2.8% vs 59.2 ± 2.1%) and promoted the angiogenesis of skin flap including improved skin perfusion (803.2 ± 24.3 vs 556.3 ± 26.7 perfusion unit), increased number of CD31-positive cells, and upregulated expression of HIF-1α in vascular endothelium on postoperative day 7, compared with ASC-EVs. Conclusions: Intradermal injecting HT-ASC-EVs improve the survival of random skin flap by promoting HIF-1α-mediated angiogenesis in rat model.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Isolated From Hypoxia-Preconditioned Adipose-Derived Stem Cells Promote Hypoxia-Inducible Factor 1α–Mediated Neovascularization of Random Skin Flap in Rats

Wang

et al. 2022

Ann Plast Surg

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“…It is well known that EPCs participate in new blood vessel formation and tissue repair as precursors of endothelial cells ( Zigdon-Giladi et al, 2015 ). Emerging data have indicated that recruitment of EPCs into ischemic tissues is one of the critical events in neovascularization ( Weng et al, 2018 ). Wang et al (2016) have reported that depletion of the NAD pool links diabetic patients to impairment of EPC mobilization.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway

Wang

Bao

Hu³

et al. 2021

Front. Pharmacol.

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Lack of vascularization is directly associated with refractory wound healing in diabetes mellitus (DM). Enrichment of endothelial precursor cells (EPCs) is a promising but challenging approach for the treatment of diabetic wounds. Herein, we investigate the action of nicotinamide riboside (NR) on EPC function for improved healing of diabetic wounds. Db/db mice that were treated with NR-supplemented food (400 mg/kg/d) for 12 weeks exhibited higher wound healing rates and angiogenesis than untreated db/db mice. In agreement with this phenotype, NR supplementation significantly increased the number of blood EPCs and bone marrow (BM)-derived EPCs of db/db mice, as well as the tube formation and adhesion functions of BM-EPCs. Furthermore, NR-supplemented BM-EPCs showed higher expression of sirtuin 1 (Sirt1), phosphorylated adenosine monophosphate–activated protein kinase (p-AMPK), and lower expression of acetylated peroxisome proliferator–activated receptor γ coactivator (PGC-1α) than BM-EPCs isolated from untreated db/db mice. Knockdown of Sirt1 in BM-EPCs significantly abolished the tube formation and adhesion function of NR as well as the expression of p-AMPK and deacetylated PGC-1a. Inhibition of AMPK abolished the NR-regulated EPC function but had no effect on Sirt1 expression, demonstrating that NR enhances EPC function through the Sirt1-AMPK pathway. Overall, this study demonstrates that the oral uptake of NR enhances the EPC function to promote diabetic wound healing, indicating that NR supplementation might be a promising strategy to prevent the progression of diabetic complications.

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“…Random skin flap is a method widely applicated to repair skin defects caused by refractory wounds ( Sinha et al, 2012 ), accidental trauma damage ( Volk et al, 2019 ), cancer excisions ( Paradela et al, 2010 ), and diabetes mellitus ( Weng et al, 2018 ). However, flap necrosis, a common postoperative complication, often leads to serious consequences, thus limiting its clinical application.…”

Section: Introductionmentioning

confidence: 99%

Formononetin Improves the Survival of Random Skin Flaps Through PI3K/Akt-Mediated Nrf2 Antioxidant Defense System

Jiang

Lou

et al. 2022

Front. Pharmacol.

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Random-pattern skin flap is widely used in plastic and reconstructive surgery. However, its clinical effect is limited by ischemia necrosis occurs at the distal part of flap. Previous studies have proved that the protective effect of formononetin was associated with its antioxidant, anti-inflammatory ability. However, further research is still needed on the effect of formononetin on flap viability. The purpose of our study was to investigate the effect of formononetin on flap survival and the underlying mechanisms. Two doses (25 mg/kg, 50 mg/kg)of formononetin were administered for seven consecutive days on flap model. Flap tissues were collected on postoperative day 7. Our results revealed that formononetin promoted skin flap viability in a dose-dependent manner. Using immunohistochemical staining and western blot, we found that formononetin significantly reduced oxidative stress and inflammation. Hematoxylin and eosin (H and E) staining, laser Doppler images and immunofluorescence staining showed the enhancement of angiogenesis after formononetin treatment. Mechanistically, we demonstrated that the antioxidation of formononetin was mediated by activation and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), while down-regulating cytoplasmic Kelch-like ECH-associated protein 1 (Keap1) expression. Co-treatment with formononetin and LY294002 (15 mg/kg), a potent Phosphatidylinositol-3-kinase (PI3K) inhibitor, which aborted nuclear Nrf2 expression and phosphorylated Akt, indicating that formononetin-mediated Nrf2 activation was related to PI3K/Akt pathway. Overall, our findings revealed that formononetin increased angiogenesis, reduced oxidative stress and inflammation, thus promoting flap survival. We highlighted the antioxidant effects of formononetin since the Nrf2 system was activated. Therefore, formononetin might be a promising candidate drug that can enhance survival of skin flaps.

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All-trans retinoic acid improves the viability of ischemic skin flaps in diabetic rat models

Cited by 9 publications

References 34 publications

Extracellular Vesicles Isolated From Hypoxia-Preconditioned Adipose-Derived Stem Cells Promote Hypoxia-Inducible Factor 1α–Mediated Neovascularization of Random Skin Flap in Rats

Extracellular Vesicles Isolated From Hypoxia-Preconditioned Adipose-Derived Stem Cells Promote Hypoxia-Inducible Factor 1α–Mediated Neovascularization of Random Skin Flap in Rats

Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway

Formononetin Improves the Survival of Random Skin Flaps Through PI3K/Akt-Mediated Nrf2 Antioxidant Defense System

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