One of the main goals of California’s $3 billion stem cell research agency is to draw companies into the state so they can vie for a share of the funding.
With a recently funded $32 million initiative, the California Institute for Regenerative Medicine (CIRM) has attracted two of the biggest US players in stem cell banking to Novato, CA, to form one of the largest biobanks of induced pluripotent stem cells (iPS cells) in the world.
Cellular Dynamics International (CDI) of Madison, WI, co-founded by stem cell pioneer James Thomson, has already established a fast-growing business by selling induced pluripotent stem cells—and specialized cells derived from them such as neurons—to big pharmaceutical companies and other research customers. CDI, which recently filed a registration statement with the SEC for an initial public offering, plans to use part of the $57.2 million it hopes to raise from investors to build out a lab for the CIRM-funded iPS cell biobank.
Like embryonic stem cells, induced pluripotent stem cells can be coaxed into forming any of the specialized cells of the body. But iPS cells, which can be used for drug assays, among other purposes can be made from a skin or blood sample from any individual. This bypasses the ethical and practical constraints of deriving embryonic stem cells from very early stage human embryos, which are destroyed in the process.
At its new California outpost on the campus of the Buck Institute for Research on Aging in Novato, CDI will create iPS cells from 3,000 individuals under a $16 million grant from CIRM. Its partner, the non-profit Coriell Institute for Medical Research of Camden, NJ, will manage the repository of cells and distribute them to investigators worldwide. Coriell, which was awarded a $10 million grant from CIRM, already operates a bank of 75 iPS cell lines created in-house and by outside researchers. The balance of the $32 million will go to academic centers that will recruit donors of the tissues used to create the iPS cells.
While CIRM also supports startup companies that are trying to use stem cells to repair damaged hearts or nerves, its iPS biobank will mainly be a boost to disease investigators rather than a source of therapeutic cells.
“I look at it as opening up the human body for research,” says Coriell CEO Michael Christman. The CIRM cells will be shared with researchers, whether they work at non-profit research centers or for-profit companies. Non-profits will pay only a service charge to Coriell, but for-profits may be subject to other fees, Christman says.
From its own iPS cells, Cellular Dynamics now churns out billions of specialized cells such as cardiomyocites, neurons, and epithelial cells at its Wisconsin headquarters. Its business is based on persuading drug companies that these fully human cells make a better testing platform for the potential of their drug candidates than traditional assay methods using live animals or manipulated cell cultures from humans and animals. CDI’s customers have included Hoffman-La Roche, Eli Lilly and AstraZeneca.
CIRM’s biobank will be different from CDI’s current products because it will provide a way to study the drug responses of diseased cells, rather than “normal” ones. CDI will create iPS cell lines from people who have been diagnosed with common disorders, such as autism, Alzheimer’s disease, and cardiovascular defects. Researchers can then produce neurons from the iPS cells of an autistic child in a lab dish, for example. Those cells are expected to express at least part of the underlying abnormalities that lead to autism. Tests on these never-before-available cell types could give drug researchers a way to screen for compounds that might correct the problem, says CIRM scientific officer Uta Grieshammer.
“You can’t take brain cells from living people,” says Grieshammer. Using the cells, drug developers can also test for toxicities that might sink an otherwise promising drug candidate.
CIRM’s biobank is arising at the same time that two European consortia are also setting up large iPS cell banks: the academic-industry partnership StemBANCC, and HipSci, which will serve researchers in the UK. Each will create iPS cells from both healthy people and those diagnosed with illnesses.
Grieshammer says these biobanks will target some of the same diseases as CIRM’s, but each will probably add something unique to the research mix.
Banking and supplying iPS cells to the growing number of researchers who want to use them is increasingly becoming an industrial-scale activity rather than an informal exchange network among individual labs. Like many biobanks that facilitate this cell-sharing among scientists, Coriell originally began its New Jersey repository by accepting cell lines derived by individual researchers who didn’t have the time to exhaustively characterize them, says Christman.
“We have developed very rigorous protocols,” Christman says. For example, before sharing a cell line with other investigators, Coriell checks iPS cells for chromosomal abnormalities that may have been inadvertently introduced by the researcher who first created them.
“One wants to be able to rigorously weed those out,” he says.
CIRM’s biobank will contain 3000 iPS cell lines for distribution, plus 6000 backup lines, that were all made by the same method. Coriell will maintain records about their derivation, their genetic characteristics, the intellectual property associated with the cells, and the consent forms of people who donated tissue for each cell line.
CDI will create the iPS lines with its most advanced proprietary method, which does not insert any new genes into the cell genome. In such “footprint-free” methods, the iPS cells don’t retain any of the genes that were used to “reprogram” an original skin or blood cell into a pluripotent stem cell.
CDI is betting it can create a profitable business supplying both iPS cells and specialized cells to stem cell banks and non-profit research institutions, as well as drug firms. In its IPO registration statement, the company estimates the total market for cells used in lab experiments at $3.5 billion. The stem cell banking market is currently $1.3 billion and is expected to reach $4.4 billion by 2020, said CDI, citing research by Adivo Associates. In its preliminary IPO prospectus, the Wisconsin company said its total annual revenue grew 154 percent in 2012 to $6.6 million.
CIRM’s biobank will contain iPS cell lines from hundreds of individuals for each of the 10 diseases that are the project’s focus. CIRM will own the cells, though CDI retains the intellectual property in its patented methods for deriving iPS cells.
Grieshammer says CIRM chose to focus on diseases that are controlled by complex genetic patterns rather than disorders triggered by only a few highly expressed genes. A more complete picture of diseases caused by the cumulative effects of multiple genes could emerge from analyzing cells from hundreds of patients with the same diagnosis, she says. Each research group can use the iPS cells to create the specialized cells best suited to answer its questions—whether it be drug toxicity revealed by liver cells, or a neuron’s response to a small molecule compound.
The hope is that iPS banks will make the path toward new therapies quicker and cheaper, because better drug candidates will be chosen for clinical trials, Grieshammer says.
“If this produces one drug that can help in one kind of disease that is common, it’s worth the entire investment,” Grieshammer says.