Copenhagen Researchers Bring Hope to Millions Facing Future Breast Reconstruction | Adipose Stem Cell Expansion | Corning

There is another common procedure that’s less invasive, but still has significant shortcomings: autologous fat grafts in which fat tissue is removed from the patient’s thighs, belly, and buttocks by liposuction, processed into tissue suspension, then injected to recreate the breast. As Dr. Glovinski emphasizes, “Up to 80 percent of the injected fat can be resorbed by the body, and a lot of tissue can die. Often women need the procedure redone several times.”

But what if, the team posed, fat graft tissue could be enriched with ex vivo expanded autologous adipose-derived stem cells to increase graft viability? “We know that stem cells secrete growth factors and differentiate into mature fat cells, which may help graft survival,” explains Dr. Glovinski, who brings a rare combination of cell culture research expertise and clinical experience to the project.

In 2013, with co-sponsorship from the Danish Cancer Society, Centre of Head and Orthopaedics Rigshospitalet, and Moalem Weitemeyer Bendtsen, they initiated a triple-blind, placebo-controlled trial to compare the survival of enriched with non-enriched fat grafts. The results, published in The Lancet (Kølle, et al., 2013) were promising, indicating that ASC graft enrichment could render liposuction a reliable alternative to major tissue augmentation1. “That first clinical trial, in which enriched fat grafts were injected into the upper arms, was important as a proof of concept,” notes Dr. Glovinski.

The team has now moved ahead with a year-long clinical study that will ultimately involve female participants. The protocol involves harvesting stem cells from each woman via liposuction, then culturing the ASCs, similarly to their previous clinical study. Autologous fat grafts are then enriched with the stem cells before being injected into the breasts. The project has been registered, approved, and classified by the Danish National Health authorities as “Advanced Medical Therapy.” As Dr. Glovinski notes, “In turn, because the project was designated as advanced medical therapy, our application was also reviewed by the Danish National Scientific Committee, which, we were honored to learn, provided its approval.”

By expanding the cells ex vivo, the team knew they could improve their physiological concentration significantly. However, as Dr. Glovinski says, "Our biggest challenge was to figure out the best way to scale-up."

The researchers contacted their local Corning representative in Copenhagen to help them devise a solution for their specific needs. "It was trial by error," says Caroline Hughes Jenkins, Corning Life Sciences. "We tested 25cm² flasks with three surface types, tried Corning HYPERStack®-12 with Corning CellBIND® surface, then CellSTACK-10 coated with a Corning Tissue Culture (TC)-treated surface, which alters the surface charge of the culture vessel to improve cell attachment and growth. After a few minor adjustments, the combination of CellSTACK and TC-treated surface worked extremely well. The team is now getting more than 600 million stem cells from one CellSTACK-10 chamber."

Says Dr. Glovinski: "We chose Corning for their broad cell culture product line, which gives us everything we need for scale-up. But we had no idea of the expertise that came with the products! Caroline and her team visited our labs several times to help us find the best surface and culture vessel. They were exceptionally good at teaching us how to use the products, as well as troubleshooting when we weren't getting the yields we were anticipating."

At the completion of this trial, the researchers plan to initiate a third clinical trial – this time, with breast cancer patients. Says Dr. Glovinski: "This new technique may prove to be a game-changer in plastic surgery. Many women don't like the idea of implants or other types of invasive procedures. If they knew they could have a minimally invasive procedure using their own stem cells, we think many more women will choose reconstruction."

1. Kølle S, et al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. The Lancet. Sept 2013 382(9898):1113-1120.