Novato institute to host bank for stem cells

The Buck Institute sits high on a hill overlooking Highway 101 in Novato, a cool white structure that looks more corporate than academic, and seems distant and nest-like, perched among the oak trees and green fields.

Inside, scientists study aging and the diseases associated with getting older - Alzheimer's and Parkinson's, blindness and cancer. But in a few years, it's destined to become a hub of stem cell activity, and perhaps even priceless to the nation's scientific community.

The institute will host one of the country's first stem cell banks - a collection of disease-specific cell lines manufactured from 3,000 volunteer donors. When it opens in two or three years, the bank will distribute stem cells to scientists studying a dozen of the world's most common and complex genetic diseases.

The bank represents a huge step forward in the field of stem cell research, scientists said. It will be the first significant attempt to standardize and quality-control the manufacturing of stem cells for research. And it will break open the field of stem cell science to researchers who never before had access to the necessary tools.

"Creating a repository like this, it's going to further reinforce California as a go-to place for stem cell lines. It's going to drive a lot of research," said Brian Kennedy, chief executive officer of the Buck Institute.

Bank and laboratory

The Human Pluripotent Stem Cell Bank - the name may not be final - is being built with about $26 million in grants from the California Institute for Regenerative Medicine, the state's stem cell funding agency. The Buck Institute also has collected about $20 million from the agency to build laboratory space for a stem cell center, where the bank will be located.

Buck will host the bank, but the facility will be run by the Coriell Institute for Medical Research based in Camden, N.J. A company called Cellular Dynamics, in Madison, Wis., will be responsible for building the collection - taking tissue samples from donors and turning those samples into induced pluripotent stem (IPS) cells, which are immature, blank-slate cells that can be transformed into any other type of cell in the body.

The bank will include 9,000 total IPS cell lines - three from each of the 3,000 donors. Six hundred of the donors will be healthy adults so their cell lines can be used as controls. The other 2,400 donors will be patients with one of 12 complex genetic diseases, including autism, epilepsy, cerebral palsy, Alzheimer's and several types of heart disease, liver disease and blindness.

"The intent for these cells is research. They're for understanding better how diseases work. They're for discovering new targets for drug developers, and the cells might be used to screen for new drugs," said Uta Grieshammer, a science officer with the California Institute for Regenerative Medicine. "If these cells lead to a new drug and a new treatment, that would of course be fantastic."

Banks elsewhere

There are two other similar banks in development in the United States, both driven by the National Institutes of Health.

Japan is putting together a bank of what will be the first collection of industrialized IPS cells to be used as treatment, not research. But there are no approved uses of IPS cells in the world so far, and U.S. scientists say creating such a bank in the United States would be premature.

Since their invention in 2006 - by Japanese scientist Shinya Yamanaka, who works part-time at San Francisco's Gladstone Institutes - IPS cells have been widely embraced by scientists, both as a tool for research and as a potential therapy.

Yamanaka made his IPS cells by taking adult cells - in his case, a type of skin cell - and applying a specific sequence of chemical agents to the cells to make them regress to a stem cell state. Once a cell has been regressed, it is then capable of becoming any other cell in the body, under careful, chemical guidance in the lab.

It's their ability to become other cells that makes IPS cells so valuable. They are similar to human embryonic stem cells in that way, but IPS cells don't raise the same ethical concerns associated with embryonic research. And the number of IPS cells that can be made is limitless, unlike cells that must be culled from human embryos.

IPS cells put to use

Because IPS cells can be coaxed into other cells, they could someday be used to replace dead or damaged cells in the brain or spine, for example - treating spinal injuries or neurodegenerative diseases. Those treatments, if they ever come to be, are years, if not decades, away.

But already scientists use IPS cells to study what happens to the body in certain diseased states. By taking skin cell samples from people with Alzheimer's, for example, scientists can create neurons that exactly mimic the disease in the brain.

As the field of IPS cell research has exploded, so too has the science for making those cells - and that's become a problem. Researchers who want to use IPS cells generally have to make their own, and while some of them have used Yamanaka's original formula, many others have made adjustments to it.

That means it's difficult to compare a cell line from one lab with a line from another lab. Two scientists studying Alzheimer's in two different IPS cell lines may find different results, and have no way of knowing if those different results are due to the nature of the disease or caused by the IPS manufacturing process.

In medical research, replication is a key to scientific discovery. Any finding from one lab must be reproduced in other labs before scientists will take it as fact. If researchers can't directly compare stem cell research from one lab to another, scientific breakthroughs are going to be slow coming, if not outright impossible.

Uniformity of cells

The stem cell bank will help solve that problem. Because only one manufacturer, Cellular Dynamics, will be making all of the cell lines, scientists will be able to compare results between labs, as long as all labs take cells from the bank.

"What we can have with this stem cell bank is many, many lines that are made similarly," said Renee Reijo Pera, director of the Center for Human Embryonic Stem Cell Research and Education at Stanford. "When people make lines in their own laboratory, they characterize them differently, they induce pluripotency differently. It's hard to sort out the differences. This bank is taking out the variability from lab to lab."

Plus, the scientists who have been making IPS cells in their labs, while undoubtedly talented, usually aren't experts in cell manufacturing. They've learned how to produce cells out of necessity, but their results aren't necessarily the best quality, said Robert Palay, chief executive of Cellular Dynamics.

IPS cell development "started out with academics doing home brews," Palay said with a laugh. Since 2009, his company has been developing IPS cell lines that are sold to labs around the world, and it will manufacture on spec a stem cell line from any individual.

"There isn't the academic in the world who could afford to spend the time perfecting this that we've been able to do," he said. "This bank is about getting the better cells to do the better research."

Freeing up lab time

The bank will provide IPS cells to scientists who never had the resources to develop their own lines. And it will free up lab time for scientists who had to spend many months manufacturing a line before they could start a research project involving IPS cells.

That's a major benefit for young scientists in particular, said Pera at Stanford. She and other senior scientists can make a line of IPS cells in about three months, but for a young researcher just starting out, that process can take twice as long.

"There are clinicians and scientists who would like to study a disease, who may not have access to patients with the disease or the skills or resources to create stem cell lines," said Dr. Arnold Kriegstein, director of the Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

"Labs with available patient material can make their own lines - we've made our own lines here," Kriegstein said. "But we've also ordered lines from other sources. Right now everyone is doing whatever is most expedient to get the job done. This bank really liberates investigators. Or it will soon."

At Gladstone - where researchers often have access to IPS cells made by Yamanaka himself - scientists say they've already scaled back their production of in-house IPS cell lines, in anticipation of the bank opening in two or three years.

They'll still need to make many of their own IPS cell lines if they want to study diseases that won't be included in the bank, or if there is a particular patient with a particular genetic trait they want to examine.

"But we'll definitely decrease the number of IPS cells we are making," said Dr. Yadong Huang, an investigator at the Roddenberry Center for Stem Cell Biology and Medicine at Gladstone. "I remember six or seven years ago, when we were making IPS cells (for Alzheimer's disease), I was thinking, 'If we could get this somewhere else, we'd never do it ourselves.'

"When the bank is finished, we'll switch to use the cells from it," Huang said. "You will not only get the standardized cell lines, but you'll save the effort and time. It will be so easy to compare your results with other labs. It will be the proper way to use IPS cells."

Erin Allday is a San Francisco Chronicle staff writer. E-mail: eallday@sfchronicle.com