Pachinko Biology: Gambling on Single Cells.

Abstract

Abstract-- While stem cells hold great promise as a means of treating otherwise incurable disease due to their characteristic ability to both self-renew and differentiate, they can also play a role in disease. Chronic myeloid leukemia (CML) arises in CD34+ hematopoietic stem, and is known resistant to the tyrosine kinase inhibitors imatinib and dasatinib. Understanding the mechanism which rescue particular fractions of cells from drug-induced death requires analysis at the single cell level. We demonstrate the ability to assay the response of normal and CML stem cells to dasatinib, a small molecule drug approved for treatment of imatinib resistant CML, within a novel microfluidic platform. Dynamic, on-chip three-color viability assays reveal that difference in responses of normal and CML cell to dasatinib are observed even in the early phases of exposure, during which normal cells exhibit a significantly elevated cell death rate as compared to both controls and CML cells. However, even in the CML fraction, dasatinib markedly reduces cell migratory behaviors in all but five percent of cells. This resistant fraction may hold the key to understanding CML persistence following chemotherapeutic assault. This work demonstrates the potential utility of single cell microfluidic platform in stem cell biology.