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Stem Cell Core Facility Opens Its Doors to Salk Researchers

The smell of fresh paint and newly delivered furniture still permeated the air as Wenyuan Wang and Qian Wang arrived to feed their human embryonic stem cells (hESC) under the watchful eyes of staff scientist Travis Berggren.

A day earlier, the Wangs – who are not related – had pulled a vial of frozen hESCs from a storage tank filled with liquid nitrogen and placed them in a Petri dish. Bathed in culture medium enriched with nutrients and kept at a cozy 37 degree Celsius (98.6 degrees Fahrenheit), the cells had settled overnight and now were clamoring for fresh nutrients.

"I am not familiar with stem cells and when I look at them through the microscope it is difficult for me to tell whether they are happy or not," says Qian Wang, who mostly works with bacteria and baker's yeast. "It is important to have somebody to guide and teach us until we have enough experience ourselves."

Both Qian and Wenyuan are among the first group of young scientists being trained by Berggren to grow hESC at the Institute's new stem cell core facility. The transformation of the former storage space into a modern stem cell laboratory was made possible by a $2.3 million grant awarded to Salk last summer by the California Institute for Regenerative Medicine (CIRM) – the same organization that most recently awarded $43 million to the San Diego Consortium for Regenerative Medicine to build a separate, state-of-the-art facility where scientists from Salk, the University of California San Diego, Burnham Institute for Medical Research and the Scripps Research Institute will combine their efforts to conduct studies that will expedite discoveries and application of hESC research.

Similar to the Consortium building, the Institute's newly minted, 2,000-square-foot core facility serves as shared space for Salk scientists. In addition to being trained there, however, young researchers will also conduct studies on hESCs without the restrictions placed on federally funded stem cell research.

"It is a complete research facility much like the other cores here at Salk," says Berggren, who heads the stem cell core with lab manager Margaret Lutz (see related story on page 7). "There are a limited number of stem cell lines available for research through federal funds, but this facility is completely free of federal funding.

"We now have the space, resources and expertise for Salk researchers to not only learn how to do stem cell culture, but to also carry out experiments with human embryonic stem cells."

Program Project Director Inder Verma, professor in the Laboratory of Genetics, submitted the grant proposal and planned the facility's layout with Garry Van Gerpen, vice president of Scientific Services.

"When we started planning this facility, about one third of the Salk faculty expressed interest in working with human stem cells," says Verma. "We envisioned that it would serve as a primer for people to get interested and that it would be a place where they could learn how to grow and manipulate stem cells, and from there they could move forward to do what they like to do."

An important aspect of the new facility is the ability it provides to produce lentiviral vectors to deliver genes into cells. Originally developed for gene therapeutic purposes by Verma and his team, the technology will play a central role in the reprogramming of adult human cells (such as skin cells) back into so-called induced pluripotent stem (iPS) cells that appear to mimic hESCs in terms of appearance and behavior.

A simple skin biopsy can serve as starting material for the generation of iPS cells, raising the hope that one day reprogramming might fulfill the promise of patient specific hESCs in research and medicine without having to negotiate the ethical minefield of working with human eggs and early embryos.

Historically, hESCs have been derived from the inner cell mass of mammalian blastocysts – the balls of cells that develop after fertilization and go on to form a developing embryo.

Since the initial reports of iPS cells caused a media stir last November, several independent studies have confirmed that reprogramming is a valid method for generating human pluripotent stem cells from adult cells.

To turn regular skin cells into versatile stem cells, researchers use viral vectors to slip inside the genes for master regulators Oct3/4 and SOX2 with varying other genes to help the process along. After three to four weeks, a small number of cells will transmogrify into cells that look and act like the pluripotent human embryonic stem cells.

"It won't abolish the need to study human embryonic stem cells right away," cautions Berggren. "A lot of the technical details for reprogramming still haven't been worked out and researchers will need to perform a lot of experiments side by side and directly compare hESCs and iPSCs.

"But with reprogramming looking so promising, this is really the direction we want to move in for the future," Berggren says. "We are planning to establish the methods here at Salk and individual faculty members then will be able to take it wherever they need to."