Recent Advances in Cell surface Engineering Focused on Cell Therapy
Revolutionary progress in stem cell research and the potential of stem cell-based therapeutics promote the translation of cell therapy. Many studies based on stem cell-based therapies have had limited efficacy of cell therapy due to the lack of sufficient homing and survival of the injected cells at the target site. However, the scientists believe that cell surface engineering is one of the promising solutions to overcome the low therapeutic efficacy of cell therapy by introducing artificial active molecules on the cell membrane. More specifically, because cells communicate with each other and interact with their environment mainly through ligands and receptors on the cell membrane, the cell surface is controlled by the artificial introduction of molecules to regulate cell behavior to improve the effect of cell therapy. This is known as "cell surface engineering".
To date, studies have shown that the three main uses of cell surface engineering represent major breakthroughs in cell therapy. One of the major applications of cell surface engineering is the targeted delivery of therapeutic cells via the circulatory system. For example, specific molecules(CD34, P-selectin) expressed on the surface of endothelial cells (ECs) upon inflammatory can bind with the L-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) of white blood cells (WBCs), inducing WBCs tethered and rolled on inflammatory cells, and ultimately transport WBCs to inflammatory sites through ligand-receptor interaction. As another example, sLex is used to deliver cells to inflammatory sites because the key molecules ECs interact with WBCs are sialyl Lewis x tetrasaccharide (sLex) and selectin. Also, other inflammation-related molecules such as intercellular adhesion molecule (ICAM) and vascular endothelial adhesion molecule (VCAM) were applied for the targeted delivery of cells by using their specific antibody.
The second purpose aimed to enhance cellular function and organized structures to improve specific cell-cell interaction by cell surface engineering. In general, engineering of the cell membrane is to enhance presentation or sensor signal molecules by anchoring cytokine or glycosaminogly derivatives on the cell surface, such as induction of increased adhesion of mononuclear cells benefits from genetic modification of HUVEC to express modified stromal cell-derived factor 1 (SDF-1) and S1FG on the cell surface. In addition to enhancement, reducing the interaction by cell surface engineering is useful for inhibiting immune response and rejection.
For example, the cause of transplant rejection arises from Immunosuppressants produced by islet cell transplantation, but cell surface engineering can be applied to provide nonrecognizable surfaces against the immune system to avoid side effects.
Applications of the cell surface engineering described above were made by two major methods: chemical conjugation and physical insertion.
For chemical conjugation method, cells mainly communicate through membrane proteins, and the abundant amine groups on the surface of cell can be used as active sites for chemical conjugation by functionalization using N-hydroxysuccinimide (NHS) esters to conjugate at the amine groups of the cell surface. Another major approach, namely the physical method, coats the functional group on the cell membrane by hydrophobic insertion or weak ionic interaction.
For physical insertion method, the cell membrane is composed of a lipid bilayer, and the hydrophobic association between the lipid tail (fatty acid) stacks each other to form stable vesicles that enable the exogenous materials with a hydrophobic moiety to be inserted into the lipid bilayer through hydrophobic association, where is designed to engineer the surface of liposomes in drug delivery systems.
In conclusion, scientists are enthusiastic about cell surface engineering because of its function of modulating the cellular behavior for enhancing targeted delivery, cellular functions, organized structure, and immune evasion by chemical or physical modification of the cell surface. However, therapeutic outcomes by the engineered cell surface have not been very impressive, but rather limited so far. More time and effort are needed to solve these problems.
Related Services
All services are only provided for research purposes and Not for clinical use.
