Drs. Rubin and Marra Comment on Denmark Stem Cell-Enriched Fat Grafts Clinical Study
In Denmark, the first clinical study shows the potential of stem cell-enriched fat grafts to transform reconstructive surgery. McGowan Institute for Regenerative Medicine faculty members—J. Peter Rubin, MD, and Kacey Marra, PhD—weigh in on the results.
“Our promising results suggest that stem-cell enriched fat grafting might prove to be an attractive alternative to major tissue augmentation, such as breast reconstruction after cancer with allogeneic material or major tissue flap surgery, with fewer side effects and more satisfying cosmetic results”, explains Stig-Frederik Trojahn Kølle, MD, a member of the research team from Copenhagen University Hospital in Denmark, in The Lancet.
Increasingly, autologous fat grafting or lipofilling, in which an individual’s own fat is harvested to increase the volume of fat in another area of their body, is being used in reconstructive surgery, with the majority of board certified plastic surgeons in the USA who do breast reconstruction using this technique.
But despite the technique’s potential, resorption rates (the percentage of the transferred fat that does not survive) of up to 80% have been reported. Recent animal studies have shown that fat grafts enriched with culture-expanded adipose [fat]-derived stem cells (ASCs) can substantially improve graft survival.
In this study, the survival of fat grafts enriched with culture-expanded autologous ASCs was compared with traditional non-enriched fat grafts (control) in 10 healthy volunteers.
Volunteers underwent liposuction to collect fat tissue from one side of the abdomen. Two purified fat grafts were prepared for each participant and injected in the upper arms—one enriched with their own stem cells and the other without (control). The volumes of injected fat grafts were measured by MRI immediately after transplant, and just before the grafts were removed after 121 days.
The cell-treated grafts retained 80.9% of the initial volume compared with 16.3% for the control grafts, with significantly higher amounts of adipose tissue and newly formed connective tissue, and significantly less necrosis 4 months after the transplant.
According to Dr. Trojahn Kølle, “These promising results add significantly to the prospect of stem cell use in clinical settings and show that ASC graft enrichment could render lipofilling a reliable procedure, since the resorption rate, quality of tissue, and safety can be predicted.”
Writing in a linked Comment in The Lancet, J. Peter Rubin, MD, and Kacey Marra, PhD, University of Pittsburgh and McGowan Institute for Regenerative Medicine faculty members in the USA, say, “These therapies could revolutionize breast reconstruction after cancer and reconstruction of deformities after trauma, for example.”
However, they add, “A crucial open question that will affect use of this therapy is whether there is an optimum cell dose for efficacy, and/or if there is a critical threshold cell dose for therapeutic effect…Another unresolved issue for this therapy is whether high concentrations of stem cells can stimulate the growth of residual breast cancer cells…This issue will be best addressed in large clinical trials.”
Dr. Rubin said the study is “very” important.
“We’ve known that this works in animals. What’s been missing is good data on humans,” said Dr. Rubin.
These early results offer a “proof of principle,” and need to be followed up with clinical trials of actual patients, rather than healthy volunteers, Dr. Rubin said.
Dr. Rubin is chair, Department of Plastic Surgery, director of the Center for Innovation in Restorative Medicine, UPMC endowed professor of plastic surgery, and professor of bioengineering, University of Pittsburgh. Dr. Marra is associate professor, Department of Surgery, University of Pittsburgh, and director of the Plastic Surgery Laboratory as well as co-director of the Adipose Stem Cell Center.
Editorial (Adipose stem cell therapy for soft tissue reconstruction. J Peter Rubin, Kacey G Marra. The Lancet, Volume 382, Issue 9898, Pages 1077 – 1079, 28 September 2013.)
Abstract (Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. Stig-Frederik Trojahn Kølle MD, et al. The Lancet, Volume 382, Issue 9898, Pages 1113 – 1120, 28 September 2013.)