Nearly 11 years after California voters approved Proposition 71 — the California Stem Cell Research and Cures Initiative, which created the California Institute for Regenerative Medicine — the institution is hitting the high point of its reason for being.
Last month, CIRM launched the world’s largest public stem cell bank.
“The new stem cell bank is in line with CIRM’s mission of accelerating stem cell treatments to patients with unmet medical needs,” said Stephen Lin, senior science officer at CIRM. “The iPSCs (modified stem cells deposited in the bank) serve as primary models for studying the genetics of specific diseases.”
Partners in the new biobank, housed at the Buck Institute for Research on Aging in Novato, are the Coriell Institute for Medical Research, Cellular Dynamics and seven California universities, including Stanford Medical School and UC-San Francisco.
Prop. 71, approved by California voters in 2004, authorized the sale of general obligation bonds allocating $3 billion to stem cell research over 10 years. The stem cell bank is funded with a $32 million grant.
Cellular Dynamics International — known as CDI — received $16 million, Coriell received $10 million and the remainder is going to the seven academic sites charged with the responsibility of collecting blood and skin samples from thousands of individuals. Each participant undergoes rigorous consent and approval processes when donating tissue.
CDI converts cell samples into induced pluripotent stem cells that are similar to embryonic stem cells. CDI uses cells derived from skin and blood and transforms them into stem cells that have the ability to develop into all types of cells found in the human body.
For example, CDI could convert a sample into a brain cell from an autistic individual, enabling researchers to study and determine how it differs from a normal brain cell; pinpoint where the normal development path of a cell is interrupted; study how a disease develops and progresses; and test new drugs with the potential to treat autism, according to CIRM.
CDI hands off the converted cells — known as iPSCs — to the Coriell Institute for storage and distribution.
In the new bank, iPSCs will be used to study a variety of diseases, disorders and conditions, including:
- Heart, lung and liver diseases;
- Blinding eye diseases;
- Childhood neurological disorders, such as epilepsy, autism and cerebral palsy; and
- Alzheimer’s disease.
Patients with such diseases will contribute 80% of the samples, while the other 20% from healthy individuals will serve as a control group.
Where It All Begins
Stanford University, one of the seven California sites awarded grants to collect samples, is focusing on patients with a variety of diseases included in the CIRM bank’s portfolio, among them are disorders known as cardiomyopathy that affect heart muscle.
Joseph Wu, director of the Stanford Cardiovascular Institute and a professor at Stanford University Medical School, anticipates that making heart cells from these stem cells would elucidate unknown genetic predispositions to developing cardiomyopathy. He expects the work will improve understanding of new cellular processes that drive sub-types of cardiomyopathy and help identify new drug treatments targeting these unique processes. The cell bank will allow researchers to test new treatments faster and more precisely before embarking on a large, expensive clinical trial, Wu said.
Most of his study participants are patients in Stanford cardiology clinics and those referred by their physicians, along with a small number of healthy patients. He hopes to collect more than 600 samples. Each stem cell line represents one individual.
Wu is not surprised that a majority of patients agree to participate in the study once they hear about it and realize the potential benefit to the medical field.
“This informed and altruistic behavior may surprise some people who are not familiar with transnational research, but it is very much in line with our experience working with patients on research projects,” he said.
Size, Selection Distinguish New Bank
The sheer size of the bank, its careful selection of rare and common diseases its stock of high-quality, reliable cells and widespread public access to them differentiates the bank from similar efforts, according to experts.
The bank, which expects to collect 2,200 to 3,000 samples by 2017, currently has about 300.
Maria Millan, senior director of medical affairs and iPSC cell banking for CIRM, said the bank allows scientists and clinicians looking for cures for diseases to leverage the quantity and quality of iPSCs and the expertise behind their development.
“These cells provide a rich resource for patient therapy,” she said.
Thomas Novak, vice president of strategic partnerships at CDI, said, “The project allows genetically differentiated populations to be studied and to compare healthy cells with those that might have aberrant functions.” Novak said this advantage enables researchers to screen compounds to determine which ones could normalize cell function.
Besides size, broad access to iPSCs and quality control, Novak said the bank would serve as a reliable source for cells.
As a repository for the stem cells, Coriell also collects, curates and distributes de-identified clinical data, such as patient gender and whether an individual has a specific disease, which accompany each stem cell line.
“Cell lines take expertise to make, characterize and bank properly but with this new resource, research is a lot easier and could shave off months or perhaps years from a research project,” said Dorit Berlin, executive director of biobanking and scientific operations for Coriell.
“Researchers don’t have to find their own cells to study but now have a supply of quality-controlled ones available.
“Any legitimate organization can order cells for research to help develop new drug therapies or for drug screening,” Berlin said. “The cells provide lots of potential for new drug discoveries.”
Coriell catalogs all of the iPSCs in the bank and makes the listings available to researchers for ordering.
She said one vial of cells costs $750 for not-for-profit organizations and $1,500 for commercial use.
Highlighting the bank’s size, list of targeted diseases and comprehensive clinical information, Wu said, “The bank allows researchers to tackle numerous research questions that would not be possible with a small bank because it encompasses gender, racial and clinical disease breadth represented in our community and thus, makes it a very powerful research tool.”
He said the fact that the samples would be provided at cost makes this a more useful resource for researchers than other commercially available biobanks.
Not Always a Smooth Road
Although CDI is experienced in transforming human samples into iPSCs, Novak said the phenomenal number of cell lines in the new bank has generated challenges. At the top of the list is reprogramming 3,000 cell lines over a period of three years.
“This was not your average grant,” he said.
Novak said when CDI applied for its grant, the company had no idea who would be awarded grants to collect samples, making it difficult to discuss priorities in advance, such as CDI’s preference for blood over skin samples.
CDI also bumped up against budget constraints in developing standardized, affordable and validated quality control methods for converting samples into stem cells, but the company prevailed.
In addition, the project required approval from a number of review boards. Novak said the process to achieve a sign-off from so many entities has set a precedent for future projects.
CDI was not alone in facing problems. For CIRM, the biggest challenge began before partners were chosen — drawing up the request for applications that kicked off the process, said Kevin McCormack, senior director of public communications and patient advocate outreach at CIRM.
“We needed to be clear about what we are trying to do here and how it would work. That meant identifying the different elements needed to put a bank together and make it sustainable. That involved a lot of meetings and discussions with a wide variety of stakeholders to make sure we got the mix and balance right,” he said.
“As you can see there are a lot of moving parts here, particularly to get it started. Once we did that, it was a matter of waiting to see who applied and then choosing the best,” McCormack said.
Wu sees the greatest limitation as being one of logistics, either because patients do not have enough time to hear about the study or to get the necessary blood draw.