Circulating Endothelial Progenitor Cells (CEPCs)-Targeted Exosome Modification Service

The modification and production of engineered exosomes are designed to accurately target cargo to specific types of cells and tissues, which is more desirable than systemic delivery of exosomes for broad distribution to the liver and kidney. Creative Biolabs has introduced an innovative engineered exosome modification platform for delivery to circulating endothelial progenitor cells (CEPCs), allowing improved targeting to CEPCs by investigating donor cells and modifying exosome surface molecules.

Overview of CEPCs and Their Role in Vascular Endothelial Repair

CEPCs are found in the peripheral blood circulation and are strongly capable of proliferating, migrating and differentiating into mature vascular endothelial cells. Since being involved in the process of vascular neogenesis and repair after endothelial injury, CEPCs have become a research focal area in vascular tissue engineering, in vivo ischemic tissue, and vascular neogenesis of tumor tissue. As precursor cells of mature endothelial cells, CEPCs constitute an essential resource for damaged vascular endothelial cells repair in various cardiovascular diseases. Specifically, local vascular injury stimulates CEPCs to migrate home and accelerate vascular re-endothelialization, while pathological neointima formation is reduced. The key biological basis for the repair of damaged vascular endothelium and treatment of related diseases is the drug delivery system to mobilize effective CEPCs.

Fig.1 When blood vessels injured, EPCs from the bone marrow are released into the bloodstream. (Yan, 2022)

Exosome Modifications Targeting the CEPCs at Creative Biolabs

Exosome modification strategies

The most common technique for exosome modification is the construction of exosomal surface target molecules that recognize specific target receptors. Insertion of target proteins or their associated plasmids fused to exosomal membrane proteins in donor cells and then exosomes containing targeting peptides can be isolated from donor cells in post-secreted cultures. For enhancing the exosome-displayed peptide stability, the addition of a glycosylation motif at the N terminus is under consideration. Common strategies for exosome display include resorting to devices such as membrane protein LAMP-2B, CD63, and click chemical conjugation. In addition, exosomes have a natural preference for specific targeting influenced by the donor to express specific peptides and cell adhesion molecules. The capture of exosomes by specific types of recipient cells is also subject to the appropriate choice of donor source. Therefore, the engineering modification of exosomes with klotho proteins is promising for targeting CEPCs.

Engineered exosome services for targeting CEPCs

Exosome-mediated drug delivery with low toxicity, low immunogenicity, and high engineerability is used as a vehicle for the delivery of cell-free therapies. In addition, the finding that klotho gene variants are accompanied by reduced peripheral blood CEPCs indicates that the close relationship between exploring klotho proteins and CEPCs contributes to a greater understanding and treatment of diseases related to vascular endothelial injury.

Klotho proteins are designed to target CEPCs with engineering exosome modifications involving the co-receptor formation process of endocrine fibroblast growth factor (FGF). Overexpression of klotho plasmids in exosome donor cells followed by encapsulation of other drugs and/or molecules such as siRNA in the secreted exosomes has been shown to capture and endocytose klotho-modified exosomes in CEPCs. Those exosomes eventually disassemble free klotho proteins and drugs, mobilizing CEPCs to maintain patency and exert good therapeutic properties of endothelialization in chemotaxis to the site of injury.

Fig.2 Exosome-modified tissue engineered blood vessel for endothelial progenitor cell capture and targeted siRNA delivery. (Chen, 2018)

Since the precise delivery patency of natural exosomes remains unsatisfactory due to their poor targeting, Creative Biolabs has established a platform for the modification and production of exosomes modified with target proteins or target antigens. The capture of specific receptor cells with exosomes is conferred with modified surface capture molecules. It enables the precise targeting of exosomal carriers with loaded cargo to realize the requirements. Please contact us with your interest.

References

Yan, F. et al. Paracrine mechanisms of endothelial progenitor cells in vascular repair. Acta Histochem. 2022, 124(1): 151833.
Chen, W.; et al. Exosome-modified tissue engineered blood vessel for endothelial progenitor cell capture and targeted siRNA delivery. Macromol Biosci. 2018, 18(2).

Plant Exosome Isolation