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New stem cell lab

Scientists will work to define, understand and control stem cell differentiation.
Scientists will work to define, understand and control stem cell differentiation.

The Jacobs School has initiated an ambitious new research program designed to enhance the scope of the Department of Bioengineering's biomedical and biotechnology research by adding a 3,000-square-foot shared core facility for human stem cell engineering and technology development. Shu Chien, director of the UCSD Whitaker Institute of Biomedical Engineering and a university professor of bioengineering and medicine, will lead the new laboratory, which will operate as a satellite facility of the UCSD School of Medicine's Human Stem Cell Core facility.

The new lab was made possible in part with the help of a $2.8 million grant from the California Institute for Regenerative Medicine. CIRM was created after California voters in 2004 approved a ballot measure that called for $3 billion in state funding for stem cell research at universities and research institutions in the state. The CIRM grant will be used to upgrade UCSD's stem cell core and establish the new shared satellite facility in the Jacobs School, which will include labs for biomaterial synthesis and characterization, highthroughput screening, bioreactor design, and tissue engineering.

"The cell engineering core won't be trying to produce new stem cell lines, but rather carefully working to define and understand the culture conditions and growth requirements that can be used to control stem cell differentiation and fate," says Andrew McCulloch, chair of the Department of Bioengineering. "For example, we've seen that in the case of heart-muscle cells, we already know that their differentiation is influenced by electrical excitation, mechanical stiffness of the substrate, and other physical conditions found in a beating heart. We will seek to replicate those conditions in novel bioreactors in which stem cells will be grown."

Karl Willert (left), director of the UCSD School of Medicine's Human Embryonic Stem Cell Core Facility, and Andrew McCulloch, chair of the Jacobs School's Bioengineering Department.
Karl Willert (left), director of the UCSD School of Medicine's Human Embryonic Stem Cell Core Facility, and Andrew McCulloch, chair of the Jacobs School's Bioengineering Department.

The Jacobs School has earmarked $1 million in discretionary research funds as a match to the CIRM funding to remodel the shared core facility. The new lab will be used by six faculty members from the Department of Bioengineering as well as faculty from other departments across campus.

The matching funds also will be used to purchase specialized laboratory equipment that will be used by Jacobs School faculty to help understand how stem cells differentiate into heart muscle cells (McCulloch and professor Karen Christman), cells of vascular tissue (Chien and professor Shyni Varghese), chondrocyte cells in cartilage (professor Robert Sah and Varghese), neural cells (professor Gabriel Silva), and many other cell types. For example, the lab will have a LEAP™ ( laser-enabled analysis and processing) machine, technology developed by San Diego, CA-based Cyntellect Inc., to enable high-throughput imaging and manipulation of live cells.

UCSD researchers are currently investigating how stem cells might be used to treat cancer, Alzheimer's and Huntington's diseases, spinal cord injury, and other conditions that today are considered incurable by traditional means. In a hopeful sign that these cells may fulfill their promise, Dr. Martin Marsala, an associate professor in UCSD's department of anesthesiology, reported in the October 2004 issue of the European Journal of Neurosciences that rats paralyzed due to loss of blood flow to the spine returned to near normal ambulatory function six weeks after receiving grafts of human spinal stem cells.

McCulloch says lessons learned from using bioengineering approaches to control stem cells in the laboratory could be the basis for inducing a diseased or damaged tissue itself to undergo repair processes. "In no way do we imagine that the only possible outcome of stem cell research is to inject stem cells to the body to treat a medical condition," says McCulloch. "That's just one of many possibilities."

The new stem cell engineering core in the Jacobs School will be the research home for three new bioengineering faculty members; Karen Christman, Shyni Varghese, and Kun Zhang, who come to UCSD from postdoctoral fellowships at UCLA, Johns Hopkins University, and Harvard Medical School, respectively. They will bring a wide variety of novel approaches to stem cell engineering. For example, Christman and Varghese will use nanotechnology-based techniques to synthesize biomaterials designed that send differentiation signals when they come into contact with stem cells. Zhang will develop genomic technologies for understanding the signaling pathways regulating stem cells. These new faculty members will try to understand better how to manipulate such signals for therapeutic applications.

In February 2007 Chien received a $638,140 grant from CIRM to develop a high-throughput system to rapidly determine the optimum physical and chemical conditions required for stem cell differentiation into specific cell types. The ability of the bioengineering team to coax human embryonic stem cells to differentiate is considered a milestone in a larger field of study called regenerative medicine, which seeks to accelerate natural healing processes or to prompt damaged tissues to regrow.

"We will apply an array of the most promising technologies for controlling stem cell differentiation, delivering stem-cell based therapies, scaling up cell production, and engineering replacement tissues," says McCulloch. "We consider the solution of each of these technical hurdles as steps toward our goal of establishing regenerative medicine as a new paradigm of medical treatment in this century."

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