Researchers from Mount Sinai School of Medicine and two other academic institutions have received federal funding to systematically assemble functional human kidney tissue from tissue modeled on a computer. If successful, the research-which ties together several emerging technologies including virtual tissue modeling and nanofabrication-could lead to a more predictable way for researchers to engineer tissue outside the body and, consequently, to screen for new drugs.
To fund the project, called Dynamics Underlying Tissue Integrity, the National Institutes of Health (NIH) awarded a five-year, $6-million grant from its Transformative Research Projects (T-R01) program. T-R01 is a new program designed to support exceptionally innovative research initiatives whose anticipated outcomes have a major impact on broad, important problems in biomedical and/or behavioral research. T-R01 awardees-42 total this year-receive part of their funding from the American Recovery and Reinvestment Act.
The leader for this multi-principal investigator project, Ravi Iyengar, PhD, Director of the Experimental Therapeutics Institute (ETI) at Mount Sinai School of Medicine, said creation of a device for assembling tissue will require his team to solve a problem that has existed since pathologists first began examining human cells under microscopes.
"Pathologists typically characterize disease in patients by studying the shape of cells and tissues, and their diagnosis has always been largely empirical," said Dr. Iyengar, who is also Dorothy H. and Lewis Rosenstiel Professor and Chair, Pharmacology and Systems Therapeutics, and Professor of Oncological Sciences and Psychiatry, Mount Sinai School of Medicine. "No one knows why cell shapes change or the rules by which tissues are organized. We want to start getting a handle on this by studying the kidney, and doing that will require the collaboration of several different disciplines."
The scientists plan to focus on the podocyte, a specialized kidney cell that sits on the organ's basement membrane and controls the filtration of small molecules from proteins. A breach in this filtration barrier is a main cause of kidney disease that often occurs among patients with diabetes, HIV, and hypertension. African-Americans with hypertension are four times more likely than whites with hypertension to develop kidney disease, a condition that currently has no cure and can eventually necessitate dialysis.
According to Dr. Iyengar, discovering the tenets underlying tissue assembly, as he and colleagues plan to do here, and having a more predictable method for assembling tissues within a nanofabricated device, would have broad clinical impact. "Lack of engineered tissue devices in vitro, or outside the cell body, is a big impediment in testing new drugs," he said. "If this experiment works and we have a methodology to assemble these tissues within nanofabricated devices, this could become a very useful screening approach for discovery of new drugs for kidney disease."
"The efforts of Dr. Iyengar's team to better understand kidney function at the cellular level will aid therapeutics research," said Dennis S. Charney, MD, the Anne and Joel Ehrenkranz Dean of Mount Sinai School of Medicine and Executive Vice President for Academic Affairs at The Mount Sinai Medical Center. "Mount Sinai, whose infrastructure is designed to foster translational research, is tailor made for collaborative research projects such as this."