by Donna Castellone, MS, MT (ASCP) SH •
June 07, 2018
Just when you think you have heard everything, technology
comes up with something new. Engineering microvasculature-on-chip
models as research-enabling systems for hemostasis and thrombosis was presented
at the THSNA meeting by Dr. Wilbur Lam from Emory and Georgia Tech University.
The methodology is based
on using microfluidic devices to conduct experiments. This model is similar to
a computer chip but has a set of microchannels into which fluids can be
perfused using either syringe pumps or hydrostatic pressure. Using this process
enables the control of biological conditions to quantitatively analyze
hematologic and vascular processes involved in thrombosis and hemostasis.
Studies have also used
live culture of endothelial cells enabling this technology to accurately
recapitulate and integrate the interactions that occur in vivo among blood
cells, endothelial cells and factors in hemostasis. This system then allows the
inclusion or exclusion of different cell populations such as platelets, red
cells, white cells as well as coagulation proteins or inflammatory mediators. Conducted
are mechanistic studies under controlled shear conditions in which cells are
incorporated and clot formation can be visualized using brightfield and
fluorescence videomicroscopy. Studies conducted using this methodology allow
the technology to capture in vitro studies of bleeding and clotting. This can
be applied to the discovery of platforms for novel antithrombotic
technology has made devices hydrogel based or increase functionality by
incorporating mechanical components. One example used an interpenetrating poly
network with functionality of longer than one month allowing the monitoring of
processes that require a longer resolution such as clotting and fibrinolysis.
Or using a microchannel with endothelial cells and a micro engineered pneumatic
valve that simulated a vascular injury allows for visulation of plug formation
and measuring in vivo injury. Limitations of this “clot on a chip system”
involve the material and geometric properties of the devices.
One study that used this technology used a microvascular
whole blood flow model to determine the impact of the complement system on clot
formation which closely interacts with the coagulation system. It is believed
the interaction contributes to the proinflammatory and prothrombotic conditions
that contribute to the complication of thrombosis in certain disease states. Complement MASP-1 (mannan-binding
lectin-associated serine protease-1) activates coagulation factors and promotes
clot formation. Previously this was only shown in plasma based systems, this
simulation was conducted in a microfluidic system in which blood flows through micro
vessels using physiological flow and shear rates, which a chip that allows real
time evaluation of clot formation.This
closely resembles human physiology. Specific activators and inhibitors of MASP
were added to test effects on clot formation. Results demonstrated that
complement activator zymosan led to increased clot formation which was reversed
by an anti-complement pathway inhibitor.
Using this technology has
many exciting possibilities in the field of coagulation by recreating what
happens in vivo. By adding specific cell populations information can be
obtained of their role in hemostasis.