McGowan Institute for Regenerative Medicine
faculty member Kacey Marra, PhD (pictured top), assistant professor, department of surgery, co-director of the Adipose Stem Cell Center, and director of the Plastic Surgery Laboratory, University of Pittsburgh, is the principal investigator of a recently awarded National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, research grant entitled “3D Culture of Adipose Tissue for Screening Obesity-Related Drugs.” Project funds totaling $993,776 will be allocated throughout the 3-year project period. Key personnel named on the award include:
- McGowan Institute for Regenerative Medicine faculty member Joerg Gerlach, MD, PhD (pictured center right), professor, department of surgery, University of Pittsburgh, and director of the Bioreactor Group, McGowan Institute,
- McGowan Institute for Regenerative Medicine affiliated faculty member J. Peter Rubin, MD (pictured center left), associate professor of plastic surgery and co-director of the Adipose Stem Cell Center, University of Pittsburgh, and
- McGowan Institute for Regenerative Medicine faculty member Donna Stolz, PhD (pictured bottom), associate director of the Center for Biologic Imaging and associate professor in the department of cell biology and physiology, University of Pittsburgh.
The successful completion of this project will demonstrate that cell-cell contact in a 3D culture system mimicking natural adipose tissue represents an improvement over current petri-dish technologies aimed at developing high throughput assays for drug discovery.
The team has developed a novel, 3D bioreactor technology that permits the long-term culture of adipocytes, which is not possible using traditional 2D cell culture methods. In this study, they will utilize their technology to rapidly and effectively screen the effects of drugs on human adipose tissue function. The researchers will examine the function of adipocytes in both obese and non-obese patients.
One of the parameters to be studied is cytokine/adipokine expression. With the bioreactor technology, Dr. Marra and scientists are able to rapidly and easily analyze daily expression of cytokines in the media. New drugs may target cytokine expression of adipocytes. It has been shown that involved cytokine behavior in obesity includes the increased expression of, but not limited to:
- MCP-1 (monocyte chemotactic protein-1, which can recruit macrophages to adipose tissue),
- TNF-α (tumor necrosis factor-α, a pro-inflammatory mediator secreted by macrophages), and
- IL-8 (interleukin-8, a pro-inflammatory cytokine secreted by macrophages).
Also of interest is the expression of anti-inflammatory cytokines, such as IL-10 (interleukin-10).
While these mediators have been examined using human and murine adipose tissue in 2D in vitro culture, improved experimental systems are necessary to allow the development of high throughput assays for drug discovery. Therefore, the specific aims of this project are to:
- Isolate and characterize human adipose-derived stem cells from both male and female patients, age 40-60 years (non-obese vs. obese patients);
- Develop a novel, multi-compartment, hollow fiber 3D perfusion bioreactor technology for ASC culture in the 3D bioreactor;
- Utilize the 3D perfusion bioreactor system as a tool to study the effects of drug therapies on adipose function.
The initial concept for this research was assessed through a study that was funded by the Commonwealth of Pennsylvania. This “seed funding” permitted the maturation of the concept to the point that further development was conducted with financial support from Pfizer, Inc. This funding pathway permitted the further maturation of the concept so that a proposal for this award could be submitted to the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.
Illustration: McGowan Institute for Regenerative Medicine.
The Bioreactor Group
The Adipose Stem Cell Center
Bio: Dr. Kacey Marra
Bio: Dr. Joerg Gerlach
Bio: Dr. J. Peter Rubin
Bio: Dr. Donna Stolz