Dr. Isra Marei, Post-Doctoral Associate in Pharmacology at Weill Cornell Medicine – Qatar, is working toward engineering 3D vascular grafts for cardiovascular drug screening

According to the World Health Organization, cardiovascular diseases are the number one cause of death globally. They account for 17.9 million deaths per year, unfortunately, this number is expected to increase to 23.6 million by 2030. Despite being the subject of immense research and development efforts, only one drug out of every 10,000 cardiovascular drugs in development makes it to the market.

“This massive discrepancy between drugs that pass pre-clinical testing and those that actually make it to the market can be largely attributed to the lack of effective and predictive preclinical models. The available screening systems do not adequately reflect the human cardiovascular physiology,” said Dr. Isra Marei, Post-Doctoral Associate in Pharmacology at Qatar Foundation’s partner university Weill Cornell Medicine – Qatar (WCM-Q).

There is a serious need for more-predictive 3D human-based models to accelerate the development of potential new drugs. One way to do this, which is the path Dr. Marei has taken, is by making more complex models to mimic the human physiological conditions using human stem cells.

Speaking about how she got into this field, Dr. Marei said: “My interest in blood stem cells started during my Ph.D. when I used them to populate an artificial tissue made of a polymeric material to be used as a replacement for damaged heart valves. Their sheer potential coupled with the need for better cardiovascular treatments has only increased my fascination with them over time”

“All that support means I do feel a bit of pressure, but I would say it's positive pressure” Dr. Isra Marei 

“Blood vessels are essential for the development of all body systems, and play a critical role in many diseases; however, they are often neglected during drug screening,” said Dr. Marei.

She explained that potential drugs are tested on animals or using 2D cultures before moving to clinical trials. The problem is neither of these pre-clinical models adequately mimic the physiological environment of human blood vessels.

Dr. Marei’s work is focused on helping to accelerate drug development through human-based models.

Blood vessels are naturally formed of multiple layers of cells, embedded within a gelatinous material. The blood that flows through these vessels results in mechanical forces acting on the vessel wall. None of which is reflected in a 2D culture system that studies the effect of drugs on a single type of cell under isolated conditions.

While animal testing does provide a certain level of complexity, there are species differences, particularly genetic and metabolic, which means the results obtained from animal models cannot be fully adapted to humans.

“Because stem cells can be isolated from the patient, they can also be used to develop personalized drug-testing models making them a potential resource for personalized medicine”, Dr. Isra Marei

“My research aims to employ human stem cells to ‘engineer’ a 3D vascular graft through tissue engineering, which is an exciting emerging field that combines the use of biomaterials and cells to restore or repair damaged tissues.

“The way we are attempting to do this is by inducing cell self-assembly to form a 3D vascular graft. Once that is done, the graft will be used to test the effects of known cardiovascular drugs to validate the system.”

According to Dr. Marei, the use of 3D culture systems will bridge the gap in the current drug testing methods. These systems are anticipated to mimic the physiological conditions in the body much more closely than currently used 2D systems, therefore allowing for a better understanding of diseases and drugs.

“All that support means I do feel a bit of pressure, but I would say it's positive pressure”, Dr. Isra Marei

“Because stem cells can be isolated from the patient, they can also be used to develop personalized drug-testing models making them a potential resource for personalized medicine.”

Dr. Marei said she considers herself a “QNRF cultivated researcher through and through”. Her first exposure to scientific research was during her undergraduate years, wherein she participated in an Undergraduate Research Experience Program (UREP) project funded by the Qatar National Research Fund (QNRF).

Dr. Marei was one of the winners of an international award that aims to empower women in science.

“It left an unexpectedly big impact on me. Before starting it, I didn’t even know what biomedical research really meant, after it – I was absolutely confident that biomedical research was the career I wanted to pursue.”

Supported by QNRF’s Qatar Research Leadership Program, Dr. Marei then went on to pursue her postgraduate education at Imperial College London. Her current position is supported by QNRF’s Postdoctoral Research Award. “All that support means I do feel a bit of pressure, but I would say it's positive pressure, it only pushes me to do more and more every day,” said Dr. Marei.