Jongyoon Han - Mechanically stimulating stem cells
MIT biological engineering graduate student Frances Liu is studying ways to alter mechanical properties of cell environments to produce desired
Denis Paiste | Materials Processing Center
March 20, 2015
Researchers in MIT Associate Professor Krystyn J. Van Vliet's
group last year showed that three biomechanical and biophysical
markers could accurately identify the most desirable stem cells from a
mixed group of bone marrow-derived cells. Now, MIT biological
engineering graduate student Frances Liu is trying to advance that work
by understanding how to alter the stem cells’ physical environment to
get them to produce the most desirable chemical output.
The bone marrow cells secrete special chemicals called cytokines that
are needed in the body to repair bone tissue, fat tissue, and
connective tissue like cartilage. “These so-called factors that the
cells produce are associated with those tissue growth functions and
tissue repair functions,” Van Vliet says.
Liu grows bone marrow-derived stem cells and studies how those stem
cells release certain chemicals in response to mechanical interactions
with materials in their surrounding environment. “I would like to
manipulate the cells, using cell-material interactions, or synthetic
materials, to produce certain chemicals beneficial to tissue repair,”
Liu explains in the Laboratory for Material Chemomechanics at MIT.
“Right now we are in the characterization phase, quantifying which and
how much of different cytokines the cells secrete in response to
different chemical and mechanical cues that we provide. Down the line,
we aim to engineer those cytokine profiles using cell-material
interactions.” Liu, 24, is a third-year PhD student and expects to
complete her doctorate in 2017. She received her bachelor of science
degree in biomedical engineering from Brown University.
Liu is examining how various groups of stem cells differ in response
to lab-controlled changes in their environment in ways that might
be important for tissue repair in the body. "Frances is determining
the correlations between the mechanical properties of the materials the
cells interact with and the chemical factors that they produce in
response to that chemomechanical coupling," Van Vliet says.
Heterogeneous cellular factories
"You can think of the cells as factories; they're factories of
chemicals," Van Vliet explains. "One of the main ways you change the way
that factory operates is you change the material properties of its
environment. How stiff that environment is, how acidic that environment
is, how rough that environment is, all of those characteristics of the
cell's outside world can directly correlate with the chemicals that that
cell produces. We don't really understand all of why that happens yet,
but part of Frances' thesis is to understand these particular stem cells
and the subpopulations within them."
While other researchers previously studied mechanical factors such as
stiffness on the function of these mesenchymal (bone marrow-derived)
stem cells, it wasn't widely recognized that they were examining a mixed
population of cells, not a single well-defined cell population. "Some
of them were stem cells, but some were not," Van Vliet says.
One way that Liu sorts her stem cells into groups is using an
inertial microfluidic separation device that separates cells of large
diameter cells from those of small diameter. This device was adapted
from previous designs of their collaborator, MIT Professor Jongyoon Han,
as part of the interdisciplinary team that Van Vliet leads within the
Singapore-MIT Alliance for Research and Technology (SMART). The group
showed in a 2014 paper that
three markers — size, mechanical stiffness, and how much the nucleus
inside the cell moves around — are sufficient to identify stem cells in a
heterogeneous population of chemically similar but non-stem cells. "We
measured those three properties as well as several other properties, but
only those three properties together, that triplet of properties,
distinguished a stem cell from a non-stem cell," Van Vliet says.
By using the microfluidic device, we can better understand the
differences between the subpopulations of these heterogeneous bone
marrow cells and which cytokines each subpopulation may be secreting,
both in the body and in the lab.