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Injectable PLGA microspheres encapsulating WKYMVM peptide for neovascularization
Young Hwan Choi1, Soon Chul Heo2, Yang Woo Kwon2
1School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 152-742, Republic of Korea.
Abstract:
Formyl peptide receptor-2 (FPR-2) is expressed in various cell types, such as phagocytes, fibroblasts, and endothelial cells. FPR-2 has been reported to play a significant role in inflammation and angiogenic response, and synthetic WKYMVm peptide has been identified as a novel peptide agonist for the FPR-2. In this study, we demonstrate that WKYMVm peptides stimulate the angiogenic potential of outgrowth endothelial cells (OECs). Upon WKYMVm peptide exposure, migration and proliferation of OECs were stimulated. WKYMVm effectively stimulated angiogenesis in tube formation assay and aortic ring assay. Furthermore, we fabricated injectable poly (lactide-co-glycolide) (PLGA) microspheres encapsulating WKYMVm peptides, which showed sustained release of cargo molecule. When WKYMVm peptide encapsulated microspheres were injected into the hind limb ischemia model, a single injection of microspheres was as effective as multiple injections of WKYMVm peptide in restoring blood flow from ischemic injury and promoting capillary growth. These results demonstrate that sustained release of WKYMVm peptide from microspheres in the application to ischemic hind limb extended angiogenic stimulation.
Statement Of Significance:
Formyl peptide receptor (FPR) has been reported to play an important role in inflammation and angiogenic response. A synthetic WKYMVm peptide has been identified as a novel peptide activating the FPR-2 that is expressed in a various cell types, such as phagocytes, fibroblasts, and endothelial cells. In this manuscript we explored a unique property of high-affinity ligand for formyl peptide receptors-2 (FPR-2) (i.e., WKYMVm). WKYMVm-induced activation of FPR2 has been reported to be crucial in host defense and inflammation by activation of phagocytes, monocytes, and lymphocytes. In this study, highlight the efficacy of WKYMVm peptide's role in inducing neovascularization in vivo hind limb ischemia model when the peptide was released from injected PLGA microspheres in sustained manner. Our results demonstrate that sustained release of WKYMVm peptide from microspheres have extended angiogenic stimulation capacity.
Insights
WKYMVm peptide enhances blood vessel growth by activating formyl peptide receptor-2 (FPR-2). Sustained release from microspheres effectively restored blood flow in ischemic limbs, promoting capillary growth.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Vascular Biology
Background:
- Formyl peptide receptor-2 (FPR-2) is crucial for inflammation and angiogenesis.
- WKYMVm is a novel synthetic peptide agonist for FPR-2.
- Endothelial cells, including outgrowth endothelial cells (OECs), express FPR-2.
Purpose of the Study:
- To investigate the angiogenic potential of WKYMVm peptide.
- To evaluate the efficacy of WKYMVm peptide delivered via sustained-release microspheres for treating ischemic injury.
Main Methods:
- Assessed OEC migration, proliferation, and tube formation in response to WKYMVm.
- Utilized in vitro tube formation and aortic ring assays to study angiogenesis.
- Fabricated poly(lactide-co-glycolide) (PLGA) microspheres for sustained WKYMVm peptide release.
- Evaluated the therapeutic effect in a hind limb ischemia mouse model.
Main Results:
- WKYMVm peptide significantly stimulated OEC migration, proliferation, and tube formation.
- In vitro assays confirmed WKYMVm's pro-angiogenic activity.
- Injectable PLGA microspheres demonstrated sustained release of WKYMVm.
- A single injection of WKYMVm-loaded microspheres effectively restored blood flow and promoted capillary growth in ischemic hind limbs, comparable to multiple peptide injections.
Conclusions:
- WKYMVm peptide is a potent stimulator of angiogenesis.
- Sustained delivery of WKYMVm via PLGA microspheres enhances its therapeutic efficacy for ischemic conditions.
- This approach offers a promising strategy for regenerative medicine applications in ischemic diseases.
