By Pat Sherman? / Photos by Brevin Blach
Imagine a soldier who has lost a foot in combat being able to order a living replacement.
Growing organs and limbs in the lab has long been fodder for sci-fi and horror films, and the elusive dream of scientists and doctors.
But with increasing public interest and government support for stem cell research-particularly in the Golden State-that fantasy is gradually becoming reality, with groundbreaking work taking place at the UCSD Jacobs School of Engineering in La Jolla.
Professor Shu Chien, a founding chair of UCSD’s bioengineering department, says he believes that it will one day be possible to grow a replacement hand or ear using stem cells and regenerative medicine, though he is uncertain when that day will arrive.
“Sometimes science moves faster than we think,” Chien says, noting that the first draft of the human genome sequence (the genetic blueprint of the human species) was announced in 2001, nearly 10 years ahead of schedule.
“With other things, like to conquer brain cancer or brain disorders, that’s been quite a long time and we still haven’t accomplished that.”
Chien says, to grow a complete organ, scientists must first figure out how to spur stem cells to develop into specific types of tissue cells in sufficient quantity, a process known as stem cell differentiation.
Some body parts, such as internal organs including the liver or bladder, would be easier to grow than a brain or a hand, which are more complex and would be “extremely difficult” to replicate, Chien says.
Difficult indeed-skin, bone, blood vessel, muscle and nerve tissues all must come together and function synergistically to form a hand.
“The more we work on these kinds of things, the more we realize how intricate our body composition and function is,” Chien says. “There are so many different kinds of cells involved. The question is, how do we package them together to make the organ-the shape, the function and everything. For us, to recreate this (through) regenerative medicine is not an easy task, but it’s our challenge, and an opportunity.”
UCSD Bioengineering professor Shyni Varghese and her team of researchers recently created materials that mimic the chemical, mechanical and electrical cues that exist in nature, allowing stem cells to grow into specific types of tissue cells-from cardiac to bone.
During a recent visit to Varghese’s lab, assistant lab manager and UCSD graduate Susan Lin attempted to use these “bio-inspired” materials to transform human embryonic stem cells into myocytes (muscle cells), a process crucial to the treatment of muscular dystrophy.
“We’re trying to mimic (the cells'(natural) environment,” Lin says.
Like children, stem cells are temperamental and must be monitored around the clock for any changes. Varghese says Lin is good at “feeling the cells,” or examining them under a microscope to determine when they are not doing well in a particular culture (matrix) or environment.
“If you’ve worked with the cells for a long time, you can definitely see when they’re unhappy,” Varghese says. “It’s a gift.”
The type of research taking place at UCSD will help further knowledge of how to grow cardiac cells to mend damaged hearts; produce cartilage for joint repair; and create skeletal myoblasts, which are transplanted into young children with Duchenne muscular dystrophy, a disease characterized by progressive skeletal muscle degeneration.
In 2008, Varghese was awarded a $2.3 million grant from the California Institute for Regenerative Medicine to study embryonic stem cell-based transplantation therapy to treat this form of muscle disintegration.
The Matrix Reloaded
One of the factors that contribute to the growth of stem cells is the stiffness or rigidity of the culture, or matrix, on which the stem cells grow. “The work by Dr. Adam Engler in our department has shown that, if you put stem cells on a soft environment or a soft matrix, that would develop into nerve cells, which are soft,” Chien says. “If you put them in a hard matrix, it would develop into bones, which are hard tissue. The environment really has a very important influence on what the cells do.”
In Varghese’s lab, UCSD student Ameya Phadke is trying to grow bone on the surface of organic polymers.
“Right now, if you want to fix a bone, you have to cut a piece from somewhere else, like the thigh,” Phadke says. “It’s really painful, and the site that you take it from suffers. If you can make a completely synthetic, off-the-shelf material, it sort of side-steps that.”
Another promise of stem cell research is the ability to inject stem cells directly into a damaged organ, thus hastening its repair.
Dr. Karen Christman, an associate bioengineering professor at UCSD, is injecting stem cells into damaged mouse hearts to regenerate myocardial cells, which die due to oxygen deprivation during a heart attack or cardiac disease.
Researchers, such as Dr. Mark Mercola at the La Jolla branch of the Sanford-Burnham Medical Research Institute, have already grown cardiac cells.
“You can see them beating in the Petri dish, just like the heart,” Chien says. “It’s very exciting.”
Though the embryonic stem cells used in research at UCSD and other U.S. facilities are derived from discarded embryos, UCSD researchers are working to develop a way to use what are known as induced pluripotent stem cells, which are derived from adult somatic cells (such as skin).
“They have the potential to develop into almost every kind of cell in the body, and you have no religious or other kind of ethical concerns about using the embryo,” Chien says.
From the burial customs of ancient Egyptians to the proliferation of plastic surgery centers and the futuristic dream of merging man and machine, humans have long been obsessed with immortality.
While replacement body parts would contribute significantly to the longevity and quality of human life, Chien says he hopes man will never be able to realize this ultimate, narcissistic pipedream.
“Everything needs to be turned over, even our bodies,” he says. “Our cells die, and new cells come in to replace them. Society is the same way. If we have everybody living forever, what would happen to the world?
“If we have babies being born, the population would just keep on growing-and we have limited resources,” he says.
The ability to grow replacement body parts from stem cells would also put a dent in the black market for human organs, which has enticed people in poor nations to sell kidneys for as little as $3,000-and opportunistic funeral directors to remove and sell body parts without a family’s consent.
As to those who say bioengineering equates to playing god or interferes with some divine master plan, for Chien, the potential benefits of this research to mankind outweigh such considerations.
“By not treating people with a potential therapy, you’re denying the possibility of these people to be alive,” he says. “By not prolonging life, you’re cutting it short. Isn’t that something equally important to consider?”
Varghese says she believes that, within the next five to 10 years, there will be a substantial amount of progress in stem cell research.
That progress can’t occur fast enough for some. Reports of the nearly $20 million in grants UCSD has received from the California Institute for Regenerative Medicine have resulted in frequent phone calls to the department from people seeking progress reports. Varghese receives regular calls from a mother on the East Coast who has two children with muscular dystrophy.
“Every time you have to tell them, ‘Oh, I don’t know,’ it puts additional pressure on you,” she says. “I’m taking taxpayers’ money and I really want to make sure that they get some benefit out of my research.”