Tissue engineering short course showcases latest developments

Tissue engineering short course showcases latest developments

By JADE BOYD
Rice News Staff

Surgeons in Tokyo have restored the sight of 10 people by replacing damaged corneas with entirely new ones grown in a laboratory. A workman who cut off part of his thumb two years ago in Boston has a replacement that’s built around a piece of denatured coral that his body is slowly replacing with new bone. In Spain, a man with a withered hand was cured by an injection of fat cells that spurred the formation of new blood vessels and tissue in the damaged portion of the hand.

These are among the first clinical cases in tissue engineering, also known as regenerative medicine, a developing field aimed at capitalizing on the body’s natural recuperative powers.

Participants in last month’s 11th annual “Advances in Tissue Engineering” short course got an overview of all the latest developments in the field — including firsthand accounts from researchers involved in each of these pioneering trials.

Teruo Okano, director of the Institute of Advanced Biomedical Engineering and Science at Tokyo Women’s Medical University aired video of the first human surgery to use a tissue-engineered cornea.

“No sewing is required,” Okano said as the audience watched the surgeon lay the new cornea into place. “Within five minutes, the support membrane may be removed and the procedure is complete.”

Okano, who specializes in growing sheets of replacement cells, is also involved in clinical trials of replacement skin, retinas and urethral tissues. Trials of a cardiac patch are planned as well. The patch consists of four stacked sheets of heart muscle cells, each measuring just one cell deep, but several centimeters square. In animal tests, the patch has restored the pumping action of hearts damaged by heart attack.

Okano was one of 35 speakers at the four-day short course, which is held at Rice each August under the auspices of the Center for Excellence in Tissue Engineering. The course offered an overview of the latest developments in tissue engineering and attracted a diverse audience of more than 75 researchers, students, clinicians, venture capitalists and others.

“Research in tissue engineering is an interdisciplinary exercise that requires medical doctors to work with bioengineers and life scientists,” said course organizer Antonios (Tony) Mikos, the John W. Cox Professor of Bioengineering and director of Rice’s Center for Excellence in Tissue Engineering. “One of the reasons Rice invests so much time and effort in this course is because it gives our students and faculty, and our partners in the Texas Medical Center, access to some the brightest people in the field.”

All tissue engineering involves three primary components: cells, biodegradable templates for the cells to grow in — known as scaffolds — and biochemical signals and tools that cause the cells to grow or develop in a particular fashion.

“Each of us is alive because every tissue in our body automatically regenerates itself,” said Arnold Caplan, director of the Skeletal Research Center at Case Western Reserve University. “Old cells are dropping dead, and new cells are taking their place.”

For example, red blood cells only live 60-90 days. Like all other tissues in the body, they are constantly replaced by cells formed from stem cells. Stem cells, the linchpin of the body’s regenerative system, are primordial cells that have the ability to replace several specific cell types. Stem cells respond to chemical signals within the body, moving where they are needed and morphing into the type of replacement cells needed.

For example, hemopoietic stems cells are the type of stem cells that replace dying red blood cells. Caplan showed that the transformation from stem cell to red blood cell involves more than a half dozen stages of development, each initiated and guided by a set of chemical cues. The same hemopoietic cells that form red blood cells could instead develop into white blood cells, platelets or other tissues depending upon the cues they receive.

As the basic components of the body’s regenerative system, stem cells play a central role in regenerative medicine. To grow new bone, corneas or other tissues, tissue engineers start with a culture of stem cells and use the necessary chemical signals to prod the cells into becoming the type of tissue that’s need.

Caplan specializes in the study of mesenchymal stem cells (MSCs), a particularly useful variety because of its ability to form bone, bone marrow, cartilage, tendon, teeth, fat and skin. Caplan described new studies that have identified two chemical cues that combine to stunt the growth of blood vessels and encourage MSCs to form cartilage rather than bone.

Caplan said much remains unknown about the specific cues and combination of cues that cause MSCs to develop into different tissues. And the rarity of the cells also makes it difficult to get enough of them to grow tissue quickly. For example, by age 50, only one in 400,000 cells is an MSC.

Some of the major challenges tissue engineers face are finding faster ways to culture and grow these rare cells, said Alan Russell, director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. He said the recent debate about whether to use embryonic verses adult stems cells has overshadowed greater scientific challenges.

“Tissue engineering is more about the 30 things you do after you decide what cell type you’re going to use,” Russell said.

For example, engineers need a much better understanding of the differences between the developmental biology of cells inside and outside the body. Most studies to date focus on developmental cues used to grow tissues in the lab, but a completely different set of physical conditions exist inside the body. Engineers must understand how tissues develop in vivo so they can design implants that will thrive after they are transplanted into patients.

Russell said the discipline also needs new methods to stimulate the formation of blood vessels, which are needed to grow anything thicker than paper-thin sheets of cells. One of the most promising methods of stimulating vascular development involves the use of fat cells.

Dr. Marc Hedrick, associate professor or surgery and pediatrics at the UCLA School of Medicine, said fat is filled with capillaries, and studies in his lab have found that injecting fat cells into developing tissues can stimulate the formation of blood vessels. And compared to other sources of stem cells, fat is usually in ready supply.

“There’s really no other outpatient procedure where you can get two liters of tissue from a patient and send them out to pick up the kids from school,” Hedrick said, describing the typical liposuction.

Russell cautioned that economics — not just scientific challenges — lie ahead for tissue engineers. Given the current economic climate, he said researchers will find it increasingly difficult to get projects funded. And Russell said most tissue engineers have yet to overcome the significant hurdle of producing a marketable product. He cautioned the audience that investors are shying away from start-ups unless the companies have a clear idea of how to profit from their technology.

The short course was sponsored byChrysalis BioTechnology Inc., Expression Genetics Inc., LifeCell Corp. and Sciperio Inc. The course was endorsed by the Biomedical Engineering Society, Controlled Release Society, Society For Biomaterials, Tissue Engineering Society International and Biomaterials Network.