Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide.
Hongyu YanXingyan MiAdam C MidgleyXinchen DuZiqi HuangTingting WeiRuihua LiuTengzhi MaDengke ZhiDashuai ZhuTing WangGuowei FengYing ZhaoWeiye ZhangJu HeMeifeng ZhuDeling KongKai WangPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2020)
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.
Keyphrases
- endothelial cells
- vascular smooth muscle cells
- coronary artery disease
- gene expression
- cancer therapy
- percutaneous coronary intervention
- oxidative stress
- drug delivery
- angiotensin ii
- cell death
- dna methylation
- dna binding
- acute coronary syndrome
- nitric oxide
- heart failure
- binding protein
- cell proliferation
- st segment elevation myocardial infarction
- photodynamic therapy
- type diabetes
- single cell
- blood flow
- cell cycle arrest
- bone marrow
- coronary artery bypass grafting
- wound healing
- ultrasound guided
- ionic liquid
- combination therapy
- left ventricular