Abstract
This study demonstrates a novel cell manipulation microdevice for cell docking, culturing, cell-cell contact and interaction by microfluidic manipulation of heterogeneous cell suspensions. Heterogeneous cell suspensions include disparate blood cells of natural killer cells and leukemia cancer cells for immune cell transplantation therapy. However, NK cell alloreactivity from different healthy donors present various recovery response levels. Little is still known about the interactions and cytotoxicity effects between donor NK cells and recipient cancer cells. The cell-based micro device first showed the capability of cell docking, movement, contact and cell-cell interaction with respect to cell cytotoxicity of NK cells against cancer cells. With various flow tests for live cell loading, flow rates of 10 μL/h were chosen for injection in the central and side flows such that both types of suspension cells could be gently docked at the gap structure in a reaction zone. The trapping number of particles and cells was linearly proportional to the gap length. Finally, the cytotoxicity of around 40% was found to be similar in the case of dilute cells and a large cell population. As a result, the cell manipulation microdevice has been validated for live suspensions of natural killer and cancer cells, and exhibited the capability to measure the cytotoxicity of dilute cell suspensions.
Highlights
There is growing awareness that natural killer cell transplantation therapy has the potential to be an effective treatment for some cancer diseases
This study proposes a cell-based microdevice that provides a platform for cell assessment of the interaction between effector natural killer (NK) cells and target cancer cells
With the cytotoxicity of NK cells against cancer cells, the cell manipulation microdevice has been preliminarily validated for such a specific effector to target ratio
Summary
There is growing awareness that natural killer cell transplantation therapy has the potential to be an effective treatment for some cancer diseases. There is only a 25% chance that one will inherit all the same HLA haplotypes from the parents This approach restricts donor selection, resulting in its limited applications. Natural killer (NK) cell transplantation is still a developing therapy approach, it is expected to decrease the risk of relapse after treatment. NK cells do not require a HLA match, unlike the transplantation of hematopoietic stem cells. This study proposes a cell-based microdevice that provides a platform for cell assessment of the interaction between effector NK cells and target cancer cells. Cell-cell interactions can be monitored in real-time for investigation of cell activity and cytotoxicity
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