New Program Examines Stem Cells' Potential To Repair, Replace Damaged Tissue

Better understanding the natural course of how stem cells live and die is the place researchers will start, says Dr. Carlos M. Isales, endocrinologist and chief of the new program in the Institute of Molecular Medicine and Genetics.

“We want to learn more about stem cells over the lifetime of a human and why they seem to quit working as we age,” says Dr. Isales of the multidisciplinary, multi-institutional group he's putting together. “Is it because the stem cells are becoming depleted. Is it because stem cells are dying out and not being replaced? Is it because you have other hormones being produced that interfere with the action of stem cells?”

To pursue answers, the program's growing faculty cuts across MCG schools as well as other universities and facilities to include MCG Schools of Medicine and Dentistry, the University of Georgia, the University of South Carolina, Savannah River National Laboratory and Fort Gordon. The group includes both clinicians and basic researchers working together to develop new approaches to treating common diseases. That group is now meeting weekly, preparing application for a Program Project grant from the National Institutes of Health which already has a name: “Molecular Mechanisms of Tissue Repair With Aging.”

Stem cells are relatively few in number and difficult to track in the body, so researchers will isolate cells from umbilical cord blood, bone marrow and fat and study them in vitro, Dr. Isales says. They also will examine the cells in tissue of different ages to see how they change and what responses generate new cells. “Maybe as cells age, they lose their ability to respond to vibration,” he says. “Each time you walk, for example, you are generating a vibration to your bone that helps keep that bone healthy and helps make that bone grow. The question is, ‘How some of these mechanisms change as we and our bones grow older?’”

Although relatively little is known about the function of stem cells in the body, some stem cells have been better characterized than others, such as mesenchymal stem cells that can become either fat, bone or cartilage. So if bone repair is the goal, it makes sense to use these, Dr. Isales says. Embryonic stem cells, which have generated much controversy, seem to have the broadest potential. These undifferentiated stem cells can make pretty much any type of tissue depending on the setting in which they are placed, many scientists agree.

“The idea is that eventually you could replace just about any tissue that is damaged,” says Dr. Isales, who wants the center's research to readily translate to better care for patients. “There are animals that regenerate whole tissues, such as salamanders that can grow new tails. Why can they and why can't we?” says Dr. Isales.

The idea of regeneration in humans has always existed to some extent, he says, but now scientists have the tools to start making it happen. “So there is potential here – when a patient needs a kidney transplant or when you have a patient with burns who needs skin grafts – the possibilities are endless,” he says.

Dr. Karl H. Wenger, a biomedical engineering scientist who is director of research for the MCG Department of Orthopaedic Surgery, will develop a bioreactor where stem cells from one of these patients could one day be grown into needed replacement organs and tissue. Each cell type has a distinct framework or matrix that will be used like the frame of a building to construct what's needed.

“We are moving from doing transplantation, like renal transplantation, where we have taken tissue from another person then give the recipient medication to keep the body from attacking that tissue, to being able to take primitive cells or the patient's own cells to grow the tissue he needs. We are trying to be on this cutting edge between growing these cells in an incubator and putting them back in people,” Dr. Isales says.

Up the street, MCG dental school researchers already are collaborating with colleagues at the Georgia Institute of Technology to use computer technology and X-rays to design identical replacements for bone and other facial tissue lost to cancer.

“We are working at the moment in materials, but the idea is to expand this into more compatible materials and eventually into natural tissue replacement,” says Dr. George S. Schuster, associate dean for research for the School of Dentistry. Dentists have been using the concept for years, taking molds or X-rays of teeth then making caps or crowns to restore form and function. “It's a very important area,” he says of the interest in regeneration. “What we are particularly interested in is being able to reconstruct people with facial cancer. Oral facial cancer is one of the most disfiguring diseases you can think of,” Dr. Schuster says of the cancer that often is found by dentists and can be very deadly if not treated aggressively.

Dental faculty, such as Dr. Schuster, with expertise in cell biology and biomaterials; Dr. James Borke, who studies bone formation; and Dr. David H. Pashley, who studies dental materials, are among those working with the new Program in Regenerative Medicine.