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USC Researchers Use Gene Therapy To Prompt Mouse Cells To Produce Human Collagen

Date:
December 24, 2002
Source:
University Of Southern California
Summary:
Researchers at the Keck School of Medicine of the University of Southern California, along with colleagues from across the country, have for the first time genetically engineered mouse cells to produce a type of human collagen--type VII--that is missing in a family of inherited skin diseases called dystrophic epidermolysis bullosa. They also prompted the mouse cells to create the structural fibers that normally arise from type VII collagen. Their work was published in the December issue of Nature Genetics.

Los Angeles, Dec. 23 –– Researchers at the Keck School of Medicine of the University of Southern California, along with colleagues from across the country, have for the first time genetically engineered mouse cells to produce a type of human collagen--type VII--that is missing in a family of inherited skin diseases called dystrophic epidermolysis bullosa. They also prompted the mouse cells to create the structural fibers that normally arise from type VII collagen. Their work was published in the December issue of Nature Genetics.

"This is the first demonstration of in vivo gene therapy where the genes have made a large extracellular molecular structure that you can actually see with a microscope," says David Woodley, M.D., professor and chief of dermatology at the Keck School and the principal investigator on this study. Scientists from Shriners Hospital for Children in Portland, Oregon, Northwestern University in Chicago, and Xgene Corporation in San Carlos, California, also participated in the study.

Woodley was helped by his previous efforts in the field: In 1992, he and some of his colleagues became the first team to clone the human gene for type VII collagen, which is one of the key components of the skin's extracellular matrix. Collagen makes up the tendrils and fibrils that provide a cushion for the skin's cells to rest upon; type VII collagen, in particular, is critical to the creation of the skin's so-called anchoring fibrils.

"Anchoring fibrils," Woodley explains, "are like connective tissue staples--they staple the epidermal layer of the skin to the dermis." Without these fibrils, the layers of the skin can separate like layers of pastry, blistering and sloughing off at the slightest insult or injury.

And that is why people without type VII collagen develop dystrophic epidermolysis bullosa, in which blisters form all over the body, leaving behind permanent scars.

"By the time people with epidermolysis bullosa are 20," says Woodley, "they often have developed very aggressive squamous cell carcinomas."

Ever since their successful cloning of the type VII collagen gene, Woodley, along with Keck School of Medicine associate professors of research Mei Chen, Ph.D., and Wei Li, Ph.D., as well as gene therapy expert Nori Kasahara, M.D., Ph.D., from USC's Institute for Genetic Medicine, has been working to insert that gene into cells that are missing it. They have been able to get the collagen gene into both fibroblasts (the cells that normally produce collagen and other fibrous tissues) and keratinocytes (the cells which normally differentiate to form the outmost layer of skin). And, in the Nature Genetics article, they have shown that these cells are capable of expressing type VII collagen and constructing anchoring fibrils in a mouse model.

Producing anchoring fibril structures in an animal, notes Chen, who is the first author on the paper, is a major step forward towards the use of gene therapy to actually treat patients with epidermolysis bullosa.

In subsequent work, Woodley adds, the engineered cells have shown that they are capable of continuing to pump out type VII collagen for at least six months--but so far, they have only done so in lab dishes. The question, of course, is whether they will be able to do the same in mice--and, eventually, in humans.

"I see patients all the time who would definitely benefit from our better understanding of the basic mechanisms of skin biology," Woodley says. "That's the goal: to help the patients who need it. Hopefully, that's what we're doing."

The research published in the Nature Genetics article was supported by grants from the National Institutes of Health.

###

Mei Chen, Noriyuki Kasahara, Douglas R. Keene, Lawrence Chan, Warren K. Hoeffler, Deborah Finlay, Maria Barcova, Paula M. Cannon, Constance Mazurek, David T. Woodley. "Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa." Nature Genetics. Vol. 32, No. 4, pp. 670-675.


Story Source:

The above story is based on materials provided by University Of Southern California. Note: Materials may be edited for content and length.


Cite This Page:

University Of Southern California. "USC Researchers Use Gene Therapy To Prompt Mouse Cells To Produce Human Collagen." ScienceDaily. ScienceDaily, 24 December 2002. <www.sciencedaily.com/releases/2002/12/021224090940.htm>.
University Of Southern California. (2002, December 24). USC Researchers Use Gene Therapy To Prompt Mouse Cells To Produce Human Collagen. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2002/12/021224090940.htm
University Of Southern California. "USC Researchers Use Gene Therapy To Prompt Mouse Cells To Produce Human Collagen." ScienceDaily. www.sciencedaily.com/releases/2002/12/021224090940.htm (accessed September 2, 2014).

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