Bone marrow on-a-chip for one step recruitment and expansion of leukemic stem cells
Oo, Nwe Nwe Linn
Date of Issue2016-05-26
School of Chemical and Biomedical Engineering
The interactions between the bone marrow (BM) niche and hematopoietic stem cells (HSC) are known to be important for the recruitment, expansion and maintenance of the HSCs. Leukemic stem cells (LSC) which show similar behavior with the BM environment are responsible for a majority of the leukemia relapse and drug resistance. This raises the importance to study these LSCs in more detail using a clinically accurate model to develop more effective patient-specific treatments. Conventional in vitro model have limited abilities to be translated into successful clinical trial results. Microfluidics are an ideal choice to provide a system to manipulate these leukemic cells in a controllable and reproducible manner while replicating the BM and LSC microenvironment, which cannot be easily achieved with conventional disease models. Here, we describe the use of bone marrow stromal cells (BMSC) to engineer a biomimetic microfluidic device using soft lithography techniques. The device comprises two side channels, housing leukemic cells and BMSC respectively, separated by a collagen “capture” channel. Leukemic cell migration into the collagen channel can be evaluated by quantifying the migration extent in the capture channel. The effect of SDF-1-CXCR4 axis inducing migration on the leukemic cells is also verified using CXCR4 antagonist. The ability to support co-culture system as well as replicate the in vivo migration behavior by selectively capturing subpopulations of LSC suggests that this device can be used as a disease model to obtain biological insights into the pathological progression relating to LSC as well as act as an accurate tool to evaluate drug efficacy during drug discovery.
Final Year Project (FYP)
Nanyang Technological University