New technology involving adipose stem cells may one day cure patients with severe wounds: Researchers

New technology developed by University of Virginia inventors involving adipose stem cells - adult stem cells found in fatty tissue - could one day be used to treat patients with severe wounds and other serious conditions.

The U.Va. Patent Foundation recently licensed a series of novel ways to identify, grow and use these cells to the GID Group, putting the U.Va. discoveries on the path to commercialization.

Over the past few years, researchers have determined that adipose stem cells have therapeutic potential in a variety of areas, including tissue engineering and treatment of chronic wounds, like those caused by diabetic ulcers; diseases characterized by poor blood flow, such as cardiac ischemia, which leads to heart attacks; and severe burns.

A collaborative team of U.Va. faculty and student investigators is taking this research a step further, developing techniques to allow adipose stem cells to realize their maximum healing potential.

"It's not just the cells you have, but how you prepare and grow them that impacts the in vivo therapeutic effect," said Dr. Adam J. Katz, a pioneer in this area and physician-scientist with joint appointments in the University's plastic surgery and biomedical engineering departments.

Traditionally, scientists seeking to prepare cells for culture will extract the cells from the body and place them on a plastic plate, where they will grow and divide. There, Katz said, the cells cannot help but interact with and adhere to their new artificial home, forming a one-layer-thick or mono-cellular carpet. In order to use the cells, this carpet structure must eventually be disrupted, impairing the cells' ability to thrive and thus their therapeutic potential.

Katz and his collaborators have adapted various techniques to create an entirely new way of culturing adipose stem cells: upside-down. Using a special inverted well plate they designed, the researchers suspend the cells in high concentration — about 50,000 cells per hanging droplet.

Under these conditions, the researchers found that the cells bind to each other rather than an artificial substance, forming a more potent, self-sufficient, three-dimensional (3-D) structure with some surprising characteristics.

"By simply enabling the cells to assemble and grow as 3-D structures, rather than 2-D mono-layers, we have found significant changes in their genetic expression, biological activity and therapeutic potential," Katz said.

Katz and his collaborators have found that these changes appear to make the 3-D cell structures more effective in treating disease. In a paper recently published in the journal Tissue Engineering, Part A, the researchers demonstrated the ability of adipose stem cells to enhance the healing of diabetic wounds in mice, particularly when the cells are prepared and delivered as 3-D spheroids.

This 3-D structuring technique serves as a platform for eight other innovative technologies developed by the researchers, including the inverted well plate and a variety of other techniques and devices used to optimize, grow and apply the cells to body tissue for wound repair and other applications.

This spring, the Patent Foundation licensed these discoveries to the GID Group, co-founded by Katz, which seeks to further develop and commercialize the technology.

"Dr. Katz and his collaborators have developed potentially game-changing technology for the treatment of diabetic wounds and other common afflictions," said Miette H. Michie, executive director and CEO of the U.Va. Patent Foundation. "We are excited to partner with the GID Group in hopes of bringing these inventive U.Va. discoveries from great science to revolutionary therapeutics."

Founded in 2009, the GID Group provides regenerative therapies based on adipose stem cells in a market expected to exceed $100B annually by 2020. The GID Group closed on its first round of funding earlier this year.

Katz was joined by several current and former U.Va. faculty, research staff and students in the invention of these novel techniques and devices, including Peter J. Amos, Edward A. Botchwey III, Moshe Khurgel, Linh N. Nguyen, Roy C. Ogle, Dr. Anna M. Parker, Shayn M. Peirce-Cottler, Margaret L. Rush, Hulan Shang, Peter C. Stapor, Blair T. Stocks and Yihwa Yang.

Stocks, a new alumnus of the biomedical engineering undergraduate program and Peirce-Cottler's lab, was the lead inventor of the inverted well plate, which enabled the investigators to scale up their research. The inexpensive and disposable tool was designed to fit seamlessly with existing cell culture plates and yield nearly 100 3-D cell structures in under 24 hours.

In developing the plate, "I cycled through the engineering design process at least a dozen times," he said. "Through each failure, I learned what I needed to improve to come closer to meeting my initial design constraints.

"I learned so much about the invention and design process through my interactions with U.Va. faculty and employees outside the lab," said Stocks, who will soon pursue a joint M.D.-Ph.D. at Vanderbilt University's School of Medicine. "Without a doubt, I know that I will be able to use the technology translation and transfer tools that the U.Va. Department of Biomedical Engineering and the Patent Foundation have given me."

SOURCE University of Virginia