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Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide.

ABSTRACT: Percutaneous coronary intervention for coronary artery disease treatment often results in pathological vascular injury, characterized by P-selectin overexpression. Adipose-derived stem cells (ADSCs) therapeutic efficacy remains elusive due to poor ADSCs targeting and retention in injured vessels. Here, conjugated P-selectin binding peptide (PBP) to polyethylene glycol-conjugated phospholipid derivative (DMPE-PEG) linkers (DMPE-PEG-PBP; DPP) are used to facilitate the modification of PBP onto ADSCs cell surfaces via hydrophobic interactions between DMPE-PEG and the phospholipid bilayer. DPP modification neither has influence on ADSCs proliferation nor apoptosis/paracrine factor gene expression. A total of 5 × 10-6 m DPP-modified ADSCs (DPP-ADSCs) strongly binds to P-selectin-displaying activated platelets and endothelial cells (ECs) in vitro and to wire-injured rat femoral arteries when administered by intra-arterial injection. Targeted binding of ADSCs shields injury sites from platelet and leukocyte adhesion, thereby decreasing inflammation at injury sites. Furthermore, targeted binding of ADSCs recovers injured ECs functionality and reduces platelet-initiated vascular smooth muscle cells (VSMCs) chemotactic migration. Targeted binding of DPP-human ADSCs to balloon-injured human femoral arteries is also demonstrated in ex vivo experiments. Overall, DPP-ADSCs promote vascular repair, inhibit neointimal hyperplasia, increase endothelium functionality, and maintain normal VSMCs alignment, supporting preclinical noninvasive utilization of DPP-ADSCs for vascular injury.

SUBMITTER: Yan H

PROVIDER: S-EPMC7284211 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide.

Yan Hongyu H Mi Xingyan X Midgley Adam C AC Du Xinchen X Huang Ziqi Z Wei Tingting T Liu Ruihua R Ma Tengzhi T Zhi Dengke D Zhu Dashuai D Wang Ting T Feng Guowei G Zhao Ying Y Zhang Weiye W He Ju J Zhu Meifeng M Kong Deling D Wang Kai K

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200422 11

Percutaneous coronary intervention for coronary artery disease treatment often results in pathological vascular injury, characterized by P-selectin overexpression. Adipose-derived stem cells (ADSCs) therapeutic efficacy remains elusive due to poor ADSCs targeting and retention in injured vessels. Here, conjugated P-selectin binding peptide (PBP) to polyethylene glycol-conjugated phospholipid derivative (DMPE-PEG) linkers (DMPE-PEG-PBP; DPP) are used to facilitate the modification of PBP onto ADS ...[more]

PMID: 32537407

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Project description:Cavernous nerve injury is the main cause of erectile dysfunction following radical prostatectomy. The recovery of erectile function following radical prostatectomy remains challenging. Our previous studies found that injecting adipose-derived stem cells (ADSCs) into the cavernosa could repair the damaged cavernous nerves, but the erectile function of the treated rats could not be restored to a normal level. We evaluated the efficacy of ADSCs infected with a lentiviral vector encoding rat brain-derived neurotrophic factor (lenti-rBDNF) in a rat model of cavernous nerve injury. The rats were equally and randomly divided into four groups. In the control group, bilateral cavernous nerves were isolated but not injured. In the bilateral cavernous nerve injury group, bilateral cavernous nerves were isolated and injured with a hemostat clamp for 2 minutes. In the ADSCGFP and ADSCrBDNF groups, after injury with a hemostat clamp for 2 minutes, rats were injected with ADSCs infected with lenti-GFP (1 × 106 in 20 ?L) and lenti-rBDNF (1 × 106 in 20 ?L), respectively. Erectile function was assessed 4 weeks after injury by measuring intracavernosal pressures. Then, penile tissues were collected for histological detection and western blot assay. Results demonstrated that compared with the bilateral cavernous nerve injury group, erectile function was significantly recovered in the ADSCGFP and ADSCrBDNF groups, and to a greater degree in the ADSCrBDNF group. Neuronal nitric oxide synthase content in the dorsal nerves and the ratio of smooth muscle/collagen were significantly higher in the ADSCrBDNF and ADSCGFP groups than in the bilateral cavernous nerve injury group. Neuronal nitric oxide synthase expression was obviously higher in the ADSCrBDNF group than in the ADSCGFP group. These findings confirm that intracavernous injection with ADSCs infected with lenti-rBDNF can effectively improve erectile dysfunction caused by cavernous nerve injury. This study was approved by the Medical Animal Care and Welfare Committee of Wuhan University, China (approval No. 2017-1638) on June 20, 2017.

Project description:BackgroundAnal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury.DesignMale rabbits were assigned to equal groups (n?=?7) including control, sphincterotomy, sphincterotomy treated with laser (660?nm, 90 s, immediately after sphincterotomy, daily, 14?days), hADSCs (2?×?106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser?+?hADSCs. Ninety?days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed.ResultsThe laser?+?hADSCs group had a higher resting pressure compared with the sphincterotomy (p?<?0.0001), laser (p?<?0.0001), and hADSCs (p?=?0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p?<?0.0001), without a significant difference between treatments (p?>?0.05). In the laser?+?hADSCs group, motor unit numbers were higher than those in the laser group (p?<?0.0001) but did not differ from the hADSCs group (p?=?0.075). Sphincterotomy increased collagen content, but the muscle content (p?=?0.36) and collagen content (p?=?0.37) were not significantly different between the laser?+?hADSCs and control groups. Laser?+?hADSCs increased ACTA1 (p?=?0.001) and MHC (p?<?0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p?=?0.009) and Ki67 mRNA expression (p?=?0.01) and decreased vimentin mRNA expression (p?<?0.0001) compared with laser.ConclusionThe combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

Dataset Information

Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide.

Publications

Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide.

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