Stem cell membrane engineering: an approach for modulating cell-biomaterial interactions

Cell membrane engineering;stem cell differentiation;tissue engineering;embryonic stem cells;biomaterials

Bansal, Nidhanjali ; Underhill ; Gregory H.

关键词: Cell membrane engineering;    stem cell differentiation;    tissue engineering;    embryonic stem cells;    biomaterials;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/50405/Nidhanjali_Bansal.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Cell membrane engineering is an emerging approach in the field of tissue engineering which aims to exploit the modification of cell membranes for a variety of applications including cell homing and retention, stem cell-tethered biosensors, and cell-mediated drug delivery. Compared to procedures requiring genetic manipulation, cell membrane engineering may exhibit several advantages such as decreased cell manipulation, a decreased effect on cell viability and proliferation, and a quicker translation towards in vivo studies. In particular, the ability to systematically manipulate the chemistry of cell membranes could form the basis for new investigations into cell functions, including most notably, the analysis of cell-microenvironment interactions. Further, the combination of cell membrane engineering with the optimization of biomaterial scaffold encapsulation techniques could potentially provide unprecedented control of cell-biomaterial interfaces which are critical in defining cellular processes such as stem cell differentiation.This Thesis describes the development and optimization of methods for the conjugation of biomaterial polymers to the membrane of pluripotent stem cells (mouse embryonic stem cells). Such methods have not previously been reported for embryonic stem cells, and thus, we aimed to establish with this work a foundation for future applications aimed at cell labeling or the defined modulation of cell functions.In order to perform quantitative analysis of stem cell membrane conjugation procedures we primarily employed a flow cytometry based approach utilizing fluorescently labeled biomaterial components. Specifically, we examined the efficiency of NHS-based biomaterial conjugation, the efficiency of an unexpected acrylate-based conjugation finding, and the combinatorial effects of UV light exposure. In addition, we systematically optimized dosage effects and explored the potential influence of biomaterial conjugation on cell viability as well as the retention of biomaterial domains during stem cell culture. The presented studies demonstrate that embryonic stem cells can be effectively modified on their cell membrane without significantly affecting cell function and expansion. Future experiments building on this work will be focused towards the further elucidation of the functional groups present on the membrane of embryonic stem cells and an improved understanding of the mechanisms underlying membrane conjugation approaches. Overall, these efforts establish a modular method for manipulating stem cells which could serve as an enabling technology for influencing stem cell functions in numerous tissue engineering contexts.