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Cell Surface Modification with Polymers for Biomedical Studies

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Modifying the living cell surface with natural and synthetic polymers provides enormous chances in the fields of biomedical engineering and science, which is an emerging technology that contributes to the study of cell-to-cell interactions and to regenerative medicine. By now, various functional groups, as well as bioactive substances, have successfully been introduced to modify the cell surface by the following means, which are covalent conjugation, hydrophobic interaction, electrostatic interaction, etc.

The paper of Yuji Teramuraa and Hiroo Iwata illustrates the approaches and polymers adopted during cell surface modification and applications in the area of biomedicine and scientific research.

Methods for cell surface modification

As is mentioned above, modifying cell surface is often realized through covalent conjugation to amino groups of cell surface proteins, hydrophobic interaction to incorporate amphiphilic polymer into the lipid bilayer membrane of cells, and electrostatic interaction between cationic polymers and a negatively charged surface.

Covalent conjugation: through covalent conjugation, the living cell surface is modified through chemical or enzymatic treatment or by metabolic introduction. There are shortcomings of this method in the specified molecule introduction and perturb cell physiology.

Hydrophobic interaction: by this method, hydrophobic alkyl chains of amphiphilic polymers are spontaneously anchored into the lipid bilayer membranes.

Electrostatic interactions: the construction of thin polymer membranes on the cell surface through electrostatic interactions could be achieved between negatively charged cell surfaces and cationic polymers. A layer-by-layer approach is then adopted for cell surface modification.

Bioactive substances: there are two streams of using bioactive substances to immobilize substances, one by intermediary molecule, and the other by forming an intermediary polymer layer through hydrophobic interactions.

Biomedical application of cell surface modification

The principal biomedical applications are in the fields of cell and organ transplantation, the study of cell-cell interactions, etc.

Cell therapy of diabetes

Bioartificial pancreas was proposed and attempted on the patients of type I diabetes who were previously treated by islets transplantation, of which the concept lies in covering the cell surface with polymer chains or thin membranes to mask cell surface antigens. The three types of bioartificial pancreases are diffusion chamber type, hollow fiber unit, and microcapsule type that was intensively researched in the past 10 years, all of which have their own strengths and drawbacks. In this review, the team achieved the following progress.

1. The level of Normoglycemia could be maintained for 1 year by combined surface modification of islets with PEG-NHS and low doses of cyclosporine A. Under low doses of cyclosporine A without PEG treatment, the Nomoglycemia could be prolonged for up to 12 days. The level of Normoglycemia could be maintained 15 days by transplanting islets that expressed Bcl-2 and were modified with PEG and albumin.

2. Immobilization of bioactive substances to the surface of islets could inhibit immediate blood mediated inflammatory reactions to improve the success rate of transplantation.

3. Successfully enclose islets with a cell layer without damaging islet function.

Blood transfusion

RBC with mPEG surface modification was proved to prevent host antibodies from recognizing ABO antigens of blood group surface, which could also prevent receptor-ligand interactions by conjugation of mPEG to the human peripheral blood mononuclear cells and murine splenocytes.

Cell-cell attachment

The control over the attachment between heterogeneous or homogeneous cells can be applied to the analysis of cell-to-cell interactions that are essential in embryo development and the research of cell therapies for various diseases, and also in stem cell differentiation into functional cells.

Conclusion:

Regarding the three approaches to modify cell surface, they all have limitations that make them only applicable for short-term use. To translate the cell surface modification based cell therapy into clinical usage, the internal mechanisms must be exactly understood and the current problems must be overcome.

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