ORLANDO — Stem cells may be the key to creating durable fat grafts and long-lasting repairs for soft tissue defects, including severe facial trauma.
In the United States, autologous fat grafting has been employed primarily for cosmetic procedures, such as facial filling and breast and buttock augmentation. However, much of the fat is resorbed within 6 months of such a procedure.
But in Europe and Asia, researchers have shown that fat grafts enriched with adipose stem cells can provide long-lasting benefits both for surgical and cosmetic patients, according to Kacey Marra, Ph.D.
Those studies have examined enriched fat transfer in breast augmentation as well as lupus-related facial atrophy, radiotherapy damage, and Crohn's fistula healing - all with very promising results, Dr. Marra said at the annual meeting of the American Academy of Cosmetic Surgery. The addition of adipose-derived stem cells encourages the fat cells to grow and form cohesive tissue, rather than dispersing into the surrounding tissues.
Some U.S. surgeons already are using stem-cell enriched fat for cosmetic surgery, said Dr. Marra, but no national studies have confirmed its safety and efficacy. The European and Asian reports "are very promising as far as safety and efficacy," but they don't provide the data needed to justify widespread adaptation of stem-cell enriched fat transfer in the United States, Dr. Marra said.
The Adipose Stem Cell Center at the University of Pittsburgh - which she directs along with Dr. J. Peter Rubin - is a leader in this area of research. Most adipose stem cell transfer includes only the stromal vascular fraction of the harvested fat, which can easily be obtained in the operating room in about an hour.
However, the stromal vascular fraction is lean when it comes to stem cells, which compose only 3%-5% of it, Dr. Marra explained.
"It's not optimal because there are so many other types of cells in it," she said in an interview. "But we can culture those stem cells into a pure population, and when we have injected them [mixed with fat] in our animal studies, we see a great potential to grow fat tissue and maintain its volume over time."
From Animals to Humans
The lab is gearing up for its first human trial in collaboration with the Department of Defense, said Dr. Rubin. The 9-month study will include 20 veterans who sustained severe facial trauma from blast injuries.
"These are severe facial injuries that involve soft tissue," Dr. Rubin said. "In most trauma patients, we can reconstruct the bony structures fairly well. But it's the soft tissue that gives us our recognizable human appearance, and that is where we have difficulty in reconstruction. These kinds of injuries have a very severe impact on people's lives."
In that early study, all of the subjects will undergo fat grafting using non-stem cell enriched fat. It's a first step to validating the techniques, Dr. Rubin said.
"One of the issues with fat grafting for any purpose is that we don't have really good data on quantifying the longevity of the grafts and the resorption over time," he said. "This will do that in a controlled fashion, using a combination of volumetric analysis and high-resolution CT scanning to assess the actual volume of the fat grafts over time."
Dr. Marra and Dr. Rubin have a follow-up study waiting in the wings. They're hoping to receive additional federal funding for a similar 9-month study of 20 more soldiers with facial injuries, who will receive fat grafts enriched with stem cells derived from the stromovascular fraction.
"Even though fat grafting has become a common procedure, there are a lot of very important questions we need to answer," Dr. Rubin said. "We need to learn the optimal way of processing the fat tissue, and we really need to get some good clinical data about the longevity of the grafts and how they hold up clinically. A lot of evidence presented is just anecdotal and hasn't been well qualified. We hope this study will provide some important benchmark data."
The Future of Fat
Getting stem cells to grow on a culture plate is one thing - getting them to grow in a body is quite another, Dr. Marra said. Her studies are advancing ways to encourage the cells to grow and develop into cohesive tissue. "We can't just inject stem cells and have them grow, she said. "We need to optimize the delivery vehicle to enhance tissue growth."
One way to do this is to provide a structure to which the stem cells can adhere. Scaffolds made from hyaluronic acid are one way. Not only do they provide a matrix for the cells, they can be loaded with growth factors to help encourage viability, differentiation, and vascularization. "We can put any growth factors we want inside them - insulin, dexamethasone, or vascular endothelial growth factor," Dr. Marra explained.