Micro-environmental Regulation of Stem Cells
David Scadden,
MD, Gerald and Darlene Jordan Professor of Medicine, Harvard University;
Co-Director, Harvard Stem Cell Institute; Co-Chair; Department of Stem
Cell and Regenerative Biology, Harvard University; Director, Center
for Regenerative Medicine, Massachusetts General Hospital,
dscadden@partners.org
Moderator: Charles A. Vacanti,
MD, Anesthesiologist-in-Chief, Leroy D. Vandam/Benjamin G. Covino Professor
of Anaesthesia, Harvard Medical School; Director, Laboratories for Tissue
Engineering and Regenerative Medicine, Brigham and Women's Hospital,
cvacanti@partners.org
David Scadden will help us explore the regulation of stem cells
by their microenvironment focusing on the hematopoietic system as a
model. Deconstructing the elements of a naturally occurring niche will
be discussed and how that information can be used in developing therapeutics
will be presented. Finally, a word of caution will be introduced by
an example of how a dysfunctional niche can lead to neoplasia.
Nudging Cells Using Molecular Interactions: Towards
Label-free Cell Rolling Separation
Rohit Karnik,
PhD, d’Arbeloff Assistant Professor, Department of Mechanical Engineering,
Massachusetts Institute of Technology,
karnik@mit.edu
Moderator: Jeffrey Borenstein, PhD, Distinguished
Member of the Technical Staff at the Charles Stark Draper Laboratory;
Co-Program Leader, Tissue Engineering, CIMIT, jborenstein@draper.com
Separation of cells using surface receptors typically relies on labeling
with fluorescent dyes or magnetic beads, or capture on surfaces. While
these approaches are extremely useful, it is desirable to minimize sample
processing for point-of-care diagnostics and for therapeutic purposes.
Rohit Karnik's lab is exploring a new method for label-free cell separation.
This approach is based on the team's discovery that asymmetrically patterned
receptor edges have the ability to nudge cells flowing over the patterns
so that they travel at an angle to the direction of fluid flow. This
effect relies on transient adhesive interactions that typically occur
during cell rolling, a physiological phenomenon exhibited by various
cell types including leukocytes, cancer cells and stem cells. As the
cell rolls on a surface in a fluid flow, bonds are formed at the leading
edge of the cell and are broken at the trailing edge. Combining cell
rolling with asymmetric receptor patterning enables control of the trajectories
of the rolling cells, and opens the possibility for label-free cell
separation where a stream of cells could be separated and collected
in a continuous-flow manner in a simple device with minimal to no sample
processing. Dr. Karnik will present results with rolling of HL-60 cells
on patterned P-selectin receptors. He will also discuss progress on
using this edge effect to realize a microfluidic device to separate
cells and our efforts on modeling of the cell rolling phenomenon. Future
development of this technology may lead to simple, label-free methods
for detection of systemic inflammation, blood counts, isolation of cancer
cells, and fractionation of stem cells.
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