Hanyang University Department of Bioengineering Professor Lee Dong-yun's joint research team developed a “cell caging” technology, which forms nanofilms on the cell surface using biopolymer multi-mix cross-linking technology with enzymes.

The “cell caging” technology prevents immune rejection responses when transplanting type 2 pancreatic cells and allowing smooth cell insulin secretion, therefore opening the possibility to treat type 1 diabetes patients without immunodepressants.

The joint research team comprised of Professor Lee, Seoul National University Professor Hwang Seok-yeon, and Professor Kim Byung-ki, succeeded in forming nanofilms using static electric gravitational pull and packing of the chitosan and hyaluronic acid, which are bio-inspired polymers. To overcome the disadvantage of the previous nanofilm packing method, which has low sustainability, the joint research team created a more firm and sustainable film by developing an actinomycete-derived S.av. tyrosinase cross-link technology. The new tyrosinase has a faster cross-linking speed compared to the previous enzyme and can be effectively used in clinical fields.

Although the thickness of the nanofilm used for enzymatic cross-linking is rather thin (140nm), it protects the cells from the immunocyte attacks caused by a physical stimulus. Formerly, alginate was widely used as a cell treatment transplant material for curing type 1 diabetes. However, as the capsule was thick, the blood sugar identification-insulin secretion was not instantaneous and involved risks of fibrosis from the immune response inducement from the alginate itself.

To solve this problem, the joint research team developed a nanofilm technology that allows instant blood sugar identification and insulin secretion by decreasing the thickness. The research team then applied the technology to a mouse pancreatic cell, the MIN6 cell, transplanted to the kidney of a type 1 diabetes mouse, and succeeded in controlling the blood sugar level. As the blood sugar control of the group with the cross-linked nanofilm was more efficient compared to the group without cross-linked nanofilm, they proved the excellence of the enzyme cross-linking technology. Additionally, it is expected that the nanofilm technology will be applicable to treating xeno-transplantation and disease treatment using stem cells, as the nanofilm technology can be used for single cells and spheroids.

Along with the international patent application of the “cell caging” technology, the joint research team was selected as the pre-startup team in the “Laboratory-specialized startup leading university project” (National Research Foundation of Korea) and “Promising biotechnology global startup support project” (Bio-I-Corps) and started research in commercialization. They are also planning to cooperate with domestic and international cell treatment development companies in the following days.

Meanwhile, the research result was published online in an international academic paper “Science Advances” in the June 23 edition. The paper is titled, “Novel Enzymatic Crosslinking-based Hydrogel Nanofilm Caging System on Pancreatic β-cell Spheroid for Long-term Blood Glucose Regulation.”