Skin-sample stem cells form new tissues

Winston-Salem, N.C. - The future of stem cell research, and ultimately therapy, may be skin deep.

Researchers at Wake Forest Institute of Regenerative Medicine report that cells taken from samples of human foreskin have formed bone, fat and muscle tissue in mice.

Previous study has shown that a single human multipotent stem cell taken from the bulge region of the follicle, when expanded in vitro and implanted into nude mice, is capable of forming epidermis, sebaceous glands and hair follicles. Now, work at the Wake Forest institute has moved that a step further.

But that earlier work produced ambiguous outcomes when cultured cells were injected into mice. Using the example of muscle cells, Dr. Atala tells Dermatology Times, "They were never really forming muscle tissue, they were just being incorporated into the existing muscle tissue" and taking on some of the properties of the host tissue.

Cells form new tissues

To definitively answer the questions of true generation of new tissue and of function, Dr. Atala's team seeded human mesenchymal stem cells onto polyglycolic acid polymer scaffolds and drove them to an adipogenic lineage in vitro before implanting the scaffolds into mice. Researchers later retrieved the structures and examined them.

"We were able to show for the first time that indeed these cells don't just have the characteristics on a tissue culture plate, they actually do form the tissues," Dr. Atala says. "This is not coming from the mouse. It proves without a doubt that the cells we are putting in are creating the tissue."

His study used bone marrow cells as controls, and both groups "had pretty much the same characteristics" in the battery of functional tests that they performed. The paper appeared in the June issue of the journal Stem Cells and Development.

The study used stem cells obtained from samples from 15 donors, ages 6 months to 24 years. Broader work has found a density of mesenchymal stem cells ranging from 0.5 percent to 1.5 percent. The source of the skin sample did not make a difference.

Clinical uses foreseen

Dr. Atala believes the first clinical use of a dermal source of stem cells is likely to be in procedures that currently use cells derived from bone barrow to repopulate blood and immune systems eradicated by radiation and chemotherapy. He says, "It would be a lot less expensive, less painful and less medically risky to take a small punch biopsy, which dermatologists do all the time," and expand those stem cells to achieve the same ends.

Wound healing is another likely early use for these techniques, he says. A small autologous sample taken from an undamaged portion of skin and expanded would avoid issues of matching tissue types and possible rejection or the use of immunosuppressant agents.

Another technical barrier to studying stem cells and ultimately moving autologous donation into practical clinical use appears to be crumbling. That is the previous inability to quickly and easily pick out stem cells residing in tissue. The key factor is "SLAM" - which stands for signaling lymphocyte activation molecule, one family of the myriad proteins that can be expressed on the surface of a cell.

"SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells" is the title of a paper in the July 1 issue of Cell by lead authors Kiel, Yilmaz and Iwashita. The International Society for Stem Cell Research singled it out as the paper of the month. The work in mouse cells was conducted at the University of Michigan.

The gold standard for identifying hematopoietic stem cells with a high degree of functional activity is to use flow cytometry and a handful of different parameters. It's a tedious and expensive process that does not lend itself to in situ use with tissue samples. The alternatives for work in tissues are not as precise, and yield a murkier picture of what is going on.