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 workload.

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.