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  F E A T U R E S  
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  The Evolution of an Ethicist  
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  Science and Politics Collide on Stem Cell Research  
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  Building Upon Our Strengths  
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 "" PHOTO — Scientists Jan A. Nolta and
Gerhard Bauer will provide key leadership for UC Davis' stem cell research program.
Scientists Jan A. Nolta and Gerhard Bauer will provide key leadership for UC Davis' stem cell research program.
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Great-grandmother and Huntington's disease patient Phyllis Hanog is looking to stem cell research to find a cure for the hereditary disease that ensnared her mother, her sister and her.

"We need stem cell research because it is what will help us find a cure for Huntington's disease and other diseases like Parkinson's," said Hanog, who lives in Livingston and participates in UC Davis clinical trials for the disease. "Our children need it."

With contributions from high-caliber scientists such as Jan A. Nolta, who is joining UC Davis to lead its stem cell program, the university is on track to take a leading role in helping to turn patients' hopes into real medical realities.

"I am extremely excited and look forward to working with the outstanding scientists and doctors at UC Davis," Nolta says. "The UC Davis commitment to the stem cell program is the strongest that I have seen."

Coming home

Nolta is joining UC Davis this fall as the stem cell research program director, pending academic senate approval. She has been scientific director of the Washington University School of Medicine Good Manufacturing Practice laboratory.

"Jan Nolta is an absolutely first-rate scientist who has earned a spot among the nation's leading stem cell researchers," says Ann Bonham, executive associate dean for research and education at the UC Davis School of Medicine. "She's the right person to build a broad-based, collaborative program that capitalizes on our many strengths. She totally 'gets' what we are about."

Part of Nolta's affinity for UC Davis comes from her past experience with the campus, which she credits as the start of her interest in stem cells.

A native of Willows, Nolta worked the night shift at the medical center's blood gas lab while pursuing her master's degree at UC Davis. She later earned her Ph.D. from University of Southern California.

Nolta became fascinated with laboratory cultures from blood and marrow, which contained a spectrum of red and white blood cells.

"To this day, I can spend hours just looking at plates of cells, wondering what mysteries lie under their membranes," she says.

The healing touch

After four years at Washington University, Nolta is returning to the one place she believes will best fulfill a bold vision: stem cell therapies for liver disease, damaged hearts and arteries, diabetes and cancer.

Her approach is to withdraw frozen stem cells from a "bank," then thaw and infuse them into injured organs and tissues.

"We have good evidence that this strategy works well," says Nolta, an editor for six research journals who has published over 200 peer-reviewed and invited academic papers.

Stem Cell Basics
Stem cells
These are cells with the ability to divide for indefinite periods without differentiating and that can either renew themselves and maintain an undifferentiated state or give rise to a variety of cell types.
Embryonic stem cells
These are primitive, or undifferentiated, cells derived from the inner cell mass of the blastocyst and that have the potential to become a wide variety of specialized cell types.
Adult (or somatic) stem cells
These are undifferentiated cells found in a particular tissue of the fetus, infant, or adult that are capable of self-renewal and provide more of the specialized cell types of the tissue from which they originate.
Hematopoietic (blood-forming) stem cells
These cells give rise to all blood cell types, including red and white blood cells and platelets.
Mesenchymal stem cells
These cells are of mesenchymal origin (embryonic connective tissue) and can differentiate toward cells that form, for example, cartilage, bone, or fat.
Neural stem and progenitor cells
These are found in some areas of the brain. They can develop into new nerve cells (neurons) or the cells that support them (glia).
Progenitor cells
Unlike stem cells that have the potential to differentiate toward a variety of cell types, progenitor cells are committed to differentiate to a defined cell type or tissue.
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Using mice whose immune systems are so deficient they can't reject transplanted human cells, Nolta's lab studies what she calls "interesting processes," such as how stem cells repair a diseased liver or withered muscle.

"New, transplanted stem cells actually 'fuse' with sick, damaged cells in some organs," she explains. "This seems bizarre, but it is actually how muscle grows naturally."

In other organs, the stem cells quickly find their way to the injured area to increase blood flow to assist the body's own repair processes.

Central to this healing touch is so-called "plasticity — the ability of a stem cell isolated from a particular tissue such as bone marrow to become a different tissue when it lands in an area of injury," Nolta explains. "Embryonic stem cells have full plasticity – the capacity to generate any and every tissue in the body."

The ability to compare human embryonic and adult stem cells in California's more research-friendly regulatory environment is particularly exciting, says Nolta. "One cell type cannot do it all, so having the ability to dissect these differences at UC Davis will be an immediate benefit. All of the tools are at hand."

From good to great

Joining Nolta from Washington University is fellow recruit Gerhard Bauer, a research lab expert who will help design and direct the new Good Manufacturing Practice (GMP) laboratory on the UC Davis Health System campus in Sacramento.

"UC Davis has committed to building quite a sophisticated GMP lab in order to take basic research discoveries directly from our lab benches into early stage clinical trials," the school's research leader Bonham explains. "Few universities have GMP labs, and we believe the facility will make us extremely attractive to other recruits and potential research partners."

An Austrian native who studied at the University of Vienna School of Medicine, "Gerhard Bauer and his expertise in designing and managing a GMP lab are critical," says Bonham.

Highly controlled and meticulously constructed to ensure quality and safety, GMP laboratories are essential to successfully obtaining FDA approval on any stem cell therapies that may emerge.

"A GMP lab needs to have controlled access; controlled temperature and humidity; controlled and validated equipment; and a controlled airflow system that supplies air with less than 10,000 particles per cubic foot per minute," explains Bauer. "In comparison, the air that we breathe in our homes contains millions of particles per cubic foot."

Bauer predicts that upon the lab's completion, UC Davis will have "probably the best GMP facility in the country, able to immediately research and derive new stem cell lines that, after certification and extensive testing, may later be used to treat patients."

While new stem cell lines are being derived, adult hematopoietic cells can be used for clinical trials as soon as the facility is completed and all the approvals are in place, Nolta said. Nolta and Bauer have completed similar work at Washington University and are transferring the technology to UC Davis.

Elegant and exciting

Often referred to as the "Harvard of the Midwest," Washington University lays claim to 22 Nobel laureates and a nearly $5 billion endowment. So, what did it take to persuade Jan Nolta, Gerhard Bauer and their research team to join UC Davis?

Current strengths that will make "UC Davis a world leader in stem cell biology" drew them, Nolta says. Strengths Nolta describes as "elegant stem cell research already ongoing; a world-renowned primate center; exciting collaborations with Shriner's Hospital and the M.I.N.D. Institute; an amazing outreach program; and cuttingedge research in genomics, proteomics, imaging technologies, cancer biology, combinatorial chemistry and biophotonics."

In other words, the building blocks of the future.

David Pleasure, director of the Institute of Pediatric Regenerative Medicine at UC Davis, says this future will arrive "relatively soon" when stem cells "grow replacement skin for children with extensive burns."

Children are particularly good candidates for stem cell therapies, Pleasure explains, because "we can reasonably anticipate that they will show more capacity to integrate skin grafts into useful tissue than older folks."

Organ transplant program director Mark Zern promises his patients a future paradigm shift: rather than transplanting whole organs from human donors, surgeons will transplant stem cells.

UC Davis' Good Manufacturing Practice Lab
The 5,160-square-foot GMP lab will be part of UC Davis' larger stem cell research facilities on Stockton Boulevard.
The GMP lab will have six manufacturing rooms for clinical grade manufacturing of cellular therapy products, recombinant DNA or gene therapy products.
Manufacturing rooms, intermediate rooms and gowning / de-gowning rooms will be isolated from each other by air pressure gradients to eliminate potential contamination.
The manufacturing rooms will be certified and maintained as Class 10,000; the intermediate rooms will be certified and maintained as Class 100,000.
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Zern's research has won him the support of Pat Anderson, the widow of Pacific Coast Building Products founder Fred Anderson who established the $1.5 million Fred and Pat Anderson Chair in Transplant Research. The Andersons' son, Jim, waited two years for a liver donation, a problem Zern says would vanish "if we could get a liver stem cell line that was immortal."

With a $6 million grant from the National Institutes of Health, professor of pediatrics and researcher Alice Tarantal leads the Center for Pediatric Stem/Progenitor Cell Translational Research, one of only two NIH centers of excellence in human translational stem cell research in the United States. She is also working with Internal Medicine Chair Frederick Meyers on a threeyear, $2.6 million Proposition 71-funded program that will train scholars in the fields of cell biology and medicine.

"As far as I know, this is the only program of its type in the U.S., and one of the most important things that drew me back to UC Davis," new research director Nolta says. "The young scientists are our future."

The big picture

Other important things that impress Nolta include the work of UC Davis medical school professors Ivan Schwab and Rivkah Isseroff to replace human corneal tissue and cure some types of blindness. Otolaryngology professor Ebenezer Yamoah sees stem cells as a therapy for deafness when they can regenerate fine hair cells in the inner ear.

Stem cells may also reverse the many diseases that affect lungs, from cancers to emphysema, says UC Davis internal medicine professor Reen Wu. "After transplantation into the blood stream, the lung traps a majority of the infused stem cells, so delivery is rapid and repair of this tissue could be robust," he says.

With a broad perspective that entails identifying what work is likely to have high scientific and medical impact, who's doing it, and then finding creative ways to bring even more here, Bonham concludes that the UC Davis commitment is clear.

"We realize the challenge to the stem cell research community is to do important and exciting laboratory-based research and – as quickly as possible – translate those findings into meaningful new therapies to cure diseases," Bonham said. "Our stem cell program is poised to do just that, building upon the existing foundation of research and looking to the future to take new and exciting advances in stem cell-mediated tissue repair to our patients who need them."

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  "We realize the challenge to the stem cell research community is to do important and exciting laboratory-based research and translate those findings into meaningful new therapies to cure  diseases." — Ann Bonham
Executive Associate
Dean for Research
and Education  
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