Blood Substitutes Based on UCSD Research
In Clinical Trialsr
Marcos Intaglietta’s dedication to
the field has been fueled by his work with governments and health
care institutions in Europe, Latin America, and Asia where many
countries have limited access to donated blood. Intaglietta
received the 2002 International Award from the Biomedical Engineering
Society for his scientific excellence and worldwide outreach.
For Bioengineering Professor Marcos Intaglietta, one of the highlights
of his career is seeing more than 20 years of research on oxygen transport
and blood substitutes come to fruition in the form of two products now
in clinical trials by UCSD spin-out Sangart, Inc. The goal—to develop
cost-effective oxygen carriers that can be used in lieu of transfused
red blood cells during episodes of temporary blood loss, such as surgery
or trauma. Sangart completed successful Phase I clinical trials in May
2002 on a blood substitute which is based on UCSD patents by Intaglietta
and Dr. Robert Winslow.
Intaglietta was the first to develop testing techniques that allow researchers
to see, measure and analyze blood flow in the microscopic blood vessels
over time in living animals. Today, his techniques and equipment are used
in labs across the country and his seminal 1998 paper on oxygen transport
is the #1 most frequently cited engineering publication on the Proceedings
of the National Academy of Sciences (PNAS) website.
Using his novel testing techniques, Intaglietta and Winslow (who was
a UCSD professor of medicine before founding Sangart) uncovered surprising
information about oxygen transport by blood substitutes. First, they found
that oxygen transport is enhanced and blood substitutes have greater efficacy
if blood viscosity is increased. Blood substitutes that are thicker and
stickier rub against the blood vessel wall, creating friction which causes
the vessel to dilate, improving blood flow and reducing the heart’s
Their second important finding was that blood substitutes should deliver
oxygen only to tissues that have an oxygen deficit, rather than releasing
as much oxygen as possible. They found that a blood substitute could be
designed to hold oxygen in reserve, only releasing oxygen to those tissues
that need it.
These counterintuitive findings by Intaglietta, an engineer, and Winslow,
a hematologist, helped explain why many of the blood substitutes under
development by biotechnology companies caused high blood pressure and
other side effects in patients. Since most blood substitutes are highly
diluted and carry oxygen in molecules dissolved in blood rather than in
red blood cells, the body’s sensory system detects the excess oxygen
and then constricts the blood vessels in an attempt to prevent too much
oxygen from reaching the tissues.
Intaglietta and Winslow have collaborated for many years in developing
a “smart” blood substitute that builds on this new information
about the microcirculation. Their work has resulted in two products now
under development by Sangart, which are aimed at providing a safe and
cost-effective alternative to donated blood.