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    Shape of things to come

    Murine models demonstrate viability of stem cell-derived, shaped and sized adipose implants


    Dr. Mao
    NEW YORK — In 2003, Jeremy Mao, D.D.S., Ph.D., began conducting research on how to use a patient's own stem cells to generate adipose tissue or grafts in specific shapes and dimensions, which he could then use to augment or reconstruct breasts. Now, he's pursuing the launch of human trials employing this novel approach.

    "We started with advances in the areas of biomaterials and stem cells, which would enable plastic and cosmetic surgeons to generate implants comparable to the sizes and dimensions of silicone gel and saline-filled implants," Dr. Mao says.

    "We have since published a number of peer-reviewed papers in tissue engineering and plastic surgery journals indicating that we are on our way to meet that original goal."

    MURINE PROVING GROUND Dr. Mao and his scientific colleagues at the University of Illinois used bone marrow to derive human mesenchymal stem cells (hMSCs), which are notable for their ability to grow into various different types of cells including adipose and cartilage cells. The researchers next preconditioned the hMSCs by exposing them for one week to an adipogenic-inducing supplement to facilitate their differentiation into adipogenic cells.

    The hMSCs were then photoencapsulated in an FDA-approved polyethylene glycol diacrylate (PEGDA) hydrogel in predefined shapes and sizes. These were then placed in the dorsum of eight laboratory mice that had been immuno-suppressed to minimize the odds for tissue rejection.Four weeks later, the implants had retained their predefined shapes and sizes and the adipose tissue graft had integrated to surrounding tissue without inflammation or other adverse reactions to the mice.

    Dr. Mao, director of the Tissue Engineering and Regenerative Medicine Laboratory at Columbia University, New York City, tells Cosmetic Surgery Times that the animal models they have utilized have limited the size of the implants to a few centimeters — clearly considerably smaller than silicone gel or saline breast implants.

    "We plan to scale up the implants when we have FDA and internal review board approval to start human studies," he says.

    THE HUMAN RENDITION In breast augmentation candidates, Dr. Mao's approach would entail obtaining the hMSCs from patients via bone marrow aspiration and expanding the stem cells multiple-fold. He would then place these cells into the biocompatible hydrogel "scaffold," transform them into the shape and dimension needed for that patient, and implant the patient's own cells at a quantity sufficient for generating a breast implant. There would be no envelope around the tissue; rather, a piece of biomaterial intended to safely disintegrate within the body as the adipose cells continued to grow.

    "The biomaterial is an engineering device that would define the shape and dimensions exactly as required," he explains. "We have a proprietary technology to shape it. So, it is not an external mold — although we could use a mold. It is more advanced than a mold."

    There would be no leakage risk, according to Dr. Mao, because the cells would be the patient's own, and once implanted, would be able to synthesize adipose tissue. As this synthesis occurred, the biomaterial would define the boundary of the implant's shape and dimension, so that the newly generated adipose tissue would remain localized. Dr. Mao acknowledges that they face a few challenges going forward, including successfully scaling up the implants so that they are comparable in size to synthetic implants, and ensuring that the stem cell implants receive adequate vascular supply.

    "The adipose-generating cells are [particularly] vascular-dependent," he observes.

    They also plan to study the longevity of the stem cell implants beyond that which they have observed thus far in murine models. While he says it is hard to predict when clinicians will have such technology at their disposal, Dr. Mao believes he will be conducting the human clinical trials within the next few years.

    References

    Alhadlaq A, Tang M, Mao JJ. Engineered adipose tissue from human mesenchymal stem cells maintains predefined shape and dimension: implications in soft tissue augmentation and reconstruction. Tissue Eng. 2005;11:556-566.

    Stosich MS, Mao JJ. Adipose tissue engineering from human adult stem cells: clinical implications in plastic and reconstructive surgery. Plast Reconstr Surg. 2007;119:71-83.

    For more information
    Jeremy Mao, D.D.S., Ph.D.
    [email protected]

    Lisette Hilton
    Lisette Hilton is a writer in Boca Raton, Fla., who heads up her company, Words Come Alive.

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