Mechanical characterization of therapeutic cells and physical property-based sorting in microfluidic systems

Du, Mingming (2017). Mechanical characterization of therapeutic cells and physical property-based sorting in microfluidic systems. University of Birmingham. Ph.D.

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Abstract

Bone marrow-derived mesenchymal and hematopoietic stem cells (MSCs and HSCs) have rapidly become the leading cells for consideration to aid tissue regeneration following injury. However, potential HSCs and MSCs migration to the injured tissue after infusion is impeded by cell trap within the upstream vessels, where physical and mechanical properties of cells play an important role. Microfluidic system has a potential to sort cells/particles based on their mechanical properties. It is hypothesized that such sorting system could be utilized to separate smaller and more deformable SCs from a cell population, infusion of which might be able to enhance the recruitment of the cells. The mechanical properties of murine HSCs were determined using micromanipulation and atomic force microscopy (AFM). Microfluidic devices were fabricated to separate sub-set of HSCs, followed by the infusion of the isolated cells into ischemia-reperfusion injured animals. HSCs as a whole became weaker and more deformable after pre-treatment with SDF-la and H 2 02, but HSC surface stiffened after the same pre-treating, accompanied by the expansion and polymerization ofF-actin interacting with the plasma membrane. A spiral microfluidic system with channel width 300m and height 40m was found to effectively isolate smaller and more deformable HSCs from a cell population, resulting in a significant increase of free flowing cells in vivo. This study comprehensively characterized cell mechanics at different levels using micromanipulation and AFM, determining mechanical markers of therapeutic cells. Most importantly, a simple cell sorting system was successfully developed to isolate target cells without introducing any chemical modification, and the possible underlying mechanism was discussed, which can be valuable to cellular therapy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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