The Study Of Endothelial Progenitor Cells’ Growth Behavior By Designing And Fabricating A Microfluidic Chip

With the application of intravascular stents in the treatment of coronary heart disease, the treatment effect was seriously challenged by the late side-effects, such as late thrombosis and in-stent restenosis. The anticoagulation and anti-hyperplasia effects of nature endothelial cells were got more attention by researchers. Hence, re-endothelialization of cardiovascular materials has become the research focus in these years. The roles of endothelial progenitor cells (EPCs) in intimal repairing and angiogenesis were realized and got more attention, and more and more researches have been done in re-endothelialization by using EPCs. However, due to the complicated environment and the difficulty of characterization, these researches were limited to study of the interaction between EPCs and materials in the static, two dimensional, single factors and separated culture platforms. The cascade and dynamic informations of cell growth behavior cannot be systematically obtained, and the in situ interaction of materials-biomimetic layers-cells cannot be observed and regulated in real-time. As one of multi-platforms, the microfluidic chip system gives an opportunity to statisfy the further study of EPCs in biology. Using a microfluidic chip, scientists can make a breakthrough in cellular microenvironment constructions with highly biomimetic structures and functions. Moreover, the growth behavior of EPCs can be dynamically studied in real-time and in situ.Six microfluidic chips with paralleled main channels, which were connected with micro channels, were designed to study the growth behavior of EPCs in the intimal repairing in this article. COMSOL software was used to simulate the spreading behaviors of fluid and stromal cell derived factor-1(SDF-1) in microfluidic chips. The results indicated that sidestream appeared in two chips because of the little width rate between the main channels and micro channels. While, the other chips performed better. The results of SDF-1diffusion showed that SDF-1distributed with density gradient in all micro channels, and the gradient decreased along with the flow direction. ECs’ adhesion, proliferation and survival behavior on polydimethylsiloxane (PDMS) were improved after treated with plasma. The same proliferation result was obtained on glass. Immunohistology results of human umbilical cord mesenchymal stem cells (HUC-MSCs), which induced by hypoxia, showed that the induced HUC-MSCs expressed the same markers as late EPCs. These EPCs can migrate to a high density place along with the SDF-1gradient. The higher SDF-1gradient is, the more obvious EPCs migration was observed. EPCs formed tube structures in a three dimensional environment supported by matrigel. The co-culture of EPCs and smooth muscle cells (SMCs) showed that both these cells can form tube structures which closely accumulate just like a vascular structure.In conclusion, microfluidic chip is a very useful and multi-functional lab platform. It can provide a three dimensional environment, mimicking the vascular structures to study of EPCs behavior in intimal repairing. It is believed that microfluidic chips have a bright prospect in the application for cardiovascular disease research.