Cell Graft Engineering Using Microfluids

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DESCRIPTION (provided by applicant): The objective of this investigation is to demonstrate proof-of-principal for a microfluidic device capable of removing dimethylsulfoxide from a cryopreserved cell suspension. Hematopoietic cells grafts (both stem cells and mature cells) have become the standard of care for a wide range of hematologic diseases. Traditional methods of stem cell cryopreservation use dimethylsulfoxide (DMSO) as a cryoprotective agent and cell grafts are routinely thawed at the patient bedside and infused directly. The clinical toxicity resulting from the infusion of DMSO into humans is well documented. Removal of DMSO using centrifugation or automated cell washers typically results in a 25-30% cell loss. Therein lies the conundrum: direct infusion of cryopreserved hematopoietic stem cells results in significant adverse reactions but washing cells to remove DMSO results in significant cell losses that, in turn, adversely affect transplant outcome. We propose a new paradigm for processing of post-thaw cell suspensions: the use of microfluidic devices. We hypothesize that microfluidic devices can be used to wash such suspensions effectively while minimizing cell losses. Liquid flows through microscale devices are characterized by low velocity, laminar flow. The cross sectional areas of the devices are small enough that the length scale can approach the diameter of blood cells (~10 micron). The laminar nature of microfluidic flow will permit diffusion-based extraction without the use of a membrane to separate fluid streams. These characteristics, combined with the possibility of fabricating massively- parallel microfluidic systems, therefore, provide an important platform from which to evaluate processing of cells in concentrations and volumes used clinically. This project also represents an important opportunity to translate our understanding of both stem cell biology and microfludics into an application that can directly benefit human health. Reducing cell losses during processing will also increase the access of stem cell based therapies (in particular cord blood stem cells) to more people.