Cellular Dynamics Announces Launch of World’s Largest Public Stem Cell Bank With 300 Available iPSC Lines

The Madison, Wisconsin-based biotechnology company, Cellular Dynamics, has announced the launch , of the world’s largest public stem cell bank and the availability of the first 300 iPSC lines.

Cellular Dynamics International, Inc. (CDI), a FUJIFILM company, has announced the launch of the world’s largest publicly available stem cell bank, the California Institute for Regenerative Medicine (CIRM) hPSC Repository.  Additionally, CDI has also announced the availability of the first 300 induced pluripotent stem cell (iPSC) lines in September, 2015.  These high quality, disease-specific iPSC resources are now accessible to academic and industry researchers to model diseases, target discovery and drug discovery.

In 2013, CDI was awarded $16 million by the CIRM to create induced pluripotent stem cell (iPSC) lines for each of 3,000 healthy and diseased volunteer donors across 11 common diseases and disorders to be made available through the CIRM hPSC Repository.

In September, the CIRM hPSC Repository will make the first 300 iPSC lines available to researchers.  These lines include cells from healthy donors and donors suffering from non-alcoholic steatohepatitis (NASH), dilated cardiomyopathy, diseases of the eye and autism.  The number of available cell lines is expected to increase to 750 by February 2016.

iPSC lines can be created from any individual, and thus provide a powerful tool for understanding disease as well as studying genetic variation between individuals. Patient samples are collected primarily from standard doctor’s office blood draws.

The iPSC lines are accompanied by detailed demographic and clinical data and each line was derived from tissue samples collected from living donors.

iPSCs have the potential to be differentiated into any cell type in the human body, and CDI already routinely manufactures 12 iPSC-derived cell types, including high-quality heart, neural, liver and endothelial cells, in high quantity, and at very high levels of purity.  Through CDI’s MyCell® Product portfolio, researchers can order iPSC line(s) of interest and have them differentiated into the cell type of choice.

Researchers can obtain undifferentiated iPSC lines through the Coriell Institute for Medical Research.

What are researchers saying about this advance:

Kaz Hirao, CDI Chairman and CEO, said, “iPSCs are proving to be powerful tools for disease modeling, drug discovery and the development of cell therapies, capturing human disease and individual genetic variability in ways that are not possible with other cellular models. We’ve seen a dramatic increase in the availability of iPSC lines. We’re pleased to be the vendor of choice for creating high quality iPSC lines and enabling scientists from academia and industry to better understand and help develop treatments for major diseases. The lines available from the CIRM stem cell bank directly complement CDI’s ability to provide differentiated cells corresponding to each of these iPSC lines, which will allow researchers to model the diseases represented, better understand disease progression, perform more targeted drug discovery, and ultimately lead to better treatments.”

Jonathan Thomas, Ph.D., J.D., CIRM Chairman, said, “We believe the bank will be an extraordinarily important resource in helping advance the use of stem cell tools for the study of diseases and finding new ways to treat them. While many stem cell efforts in the past have provided badly needed new tools for studying rare genetic diseases, this bank represents common diseases that afflict many Californians. Stem cell technology offers a critical new approach toward developing new treatments and cures for those diseases as well.”

Michael Christman, Ph.D., president and CEO of Coriell said, “Coriell Institute is a leader in managing large and complex biospecimen collections and distributing samples and data worldwide to promote research. We are very pleased to be part of this CIRM initiative and advance stem cell research for several devastating yet common diseases.”

Making Induced Pluripotent Stem Cells from a Drop of Blood

A research group in Singapore has invented a method to generate human induced pluripotent stem cells (hiPSCs) from a single drop of blood.

This method was developed by stem cell scientists at the A*STAR Institute of Molecular and Cell Biology (IMCB). This protocol enables donors to collect their own blood samples with a single pinprick, and then send to a laboratory for further processing.

The ease of collecting such a small amount of blood and deriving hiPSCs with this new technique could potentially boost the recruitment of donors, and eventually establish large stem cell-banks that have a wide diversity of donors and represent a broad cross-section of humanity.

To derive hiPSCs from mature cells, the cells are genetically engineered to express four different genes (Oct4, Sox2, Klf4 and c-Myc). The expression of these genes drives the cells to de-differentiate and reprogram themselves into embryonic-like stem cells that can, potentially, be differentiated into any mature cell type. Besides their obvious potential for regenerative medicine, hiPSCs also can serve as excellent models to test the efficacy of particular drugs and other therapies (see here for a remarkable example). Japan, the United States, and the United Kingdom all initiatives to start hiPSC banks that make hiPSCs available for research and development.

Current protocols to derive iPSCs from human blood require respectable amounts of blood. However, the IMCB protocol only calls for single-drop volumes of blood, and produces hiPSCs at very high efficiency. IMCB has filed a patent for their protocol.

Blood samples remain stable for 48 hours and can also be grown in culture for 12 days, and this extends the finger-prick method to a wide variety of geographic regions for recruitment of donors with highly varied ethnic backgrounds, genotypes and diseases.

The integration of the IMCB technique with the hiPSC stem cell initiative paves the way for establishing a stem cell bank. This could potentially completely replace embryonic stem cells.

Yuin-Han Loh from IMCB said: “It all began when we wondered if we could reduce the volume of blood used for reprogramming. Then we tested if donors could collect their own blood sample in a normal room environment and store it. Our finger-prick technique, in fact, utilized less than a drop of finger-pricked blood. The remaining blood could even be used for DNA sequencing and othe blood tests.”

Loh and his group even showed that hiPSCs derived from a a drop of blood could be differentiated into functional heart muscle cells. This illustrated the power of biobanks around the world for hiPSC studies at a scale that was previously not possible.

Vascular Progenitors Made from Induced Pluripotent Stem Cells Repair Blood Vessels in the Eye Regardless of the Site of Injection

Johns Hopkins University medical researchers have reported the derivation of human induced-pluripotent stem cells (iPSCs) that can repair damaged retinal vascular tissue in mice. These stem cells, which were derived from human umbilical cord-blood cells and reprogrammed into an embryonic-like state, were derived without the conventional use of viruses, which can damage genes and initiate cancers. This safer method of growing the cells has drawn increased support among scientists, they say, and paves the way for a stem cell bank of cord-blood derived iPSCs to advance regenerative medical research.

In a report published Jan. 20 in the journal Circulation, Johns Hopkins University stem cell biologist Elias Zambidis and his colleagues described laboratory experiments with these non-viral, human retinal iPSCs, that were created generated using the virus-free method Zambidis first reported in 2011.

“We began with stem cells taken from cord-blood, which have fewer acquired mutations and little, if any, epigenetic memory, which cells accumulate as time goes on,” says Zambidis, associate professor of oncology and pediatrics at the Johns Hopkins Institute for Cell Engineering and the Kimmel Cancer Center. The scientists converted these cells to a status last experienced when they were part of six-day-old embryos.

Instead of using viruses to deliver a gene package to the cells to turn on processes that convert the cells back to stem cell states, Zambidis and his team used plasmids, which are rings of DNA that replicate briefly inside cells and then are degraded and disappear.

Next, the scientists identified and isolated high-quality, multipotent, vascular stem cells that resulted from the differentiation of these iPSC that can differentiate into the types of blood vessel-rich tissues that can repair retinas and other human tissues as well. They identified these cells by looking for cell surface proteins called CD31 and CD146. Zambidis says that they were able to create twice as many well-functioning vascular stem cells as compared with iPSCs made with other methods, and, “more importantly these cells engrafted and integrated into functioning blood vessels in damaged mouse retina.”

Working with Gerard Lutty, Ph.D., and his team at Johns Hopkins’ Wilmer Eye Institute, Zambidis’ team injected these newly iPSC-derived vascular progenitors into mice with damaged retinas (the light-sensitive part of the eyeball). The cells were injected into the eye, the sinus cavity near the eye or into a tail vein. When Zamdibis and his colleagues took images of the mouse retinas, they found that the iPSC-derived vascular progenitors, regardless of injection location, engrafted and repaired blood vessel structures in the retina.

“The blood vessels enlarged like a balloon in each of the locations where the iPSCs engrafted,” says Zambidis. Their vascular progenitors made from cord blood-derived iPSCs compared very well with the ability of vascular progenitors derived from fibroblast-derived iPSCs to repair retinal damage.

Zambidis says that he has plans to conduct additional experiments in diabetic rats, whose conditions more closely resemble human vascular damage to the retina than the mouse model used for the current study, he says.

With mounting requests from other laboratories, Zambidis says he frequently shares his cord blood-derived iPSC with other scientists. “The popular belief that iPSCs therapies need to be specific to individual patients may not be the case,” says Zambidis. He points to recent success of partially matched bone marrow transplants in humans, shown to be as effective as fully matched transplants.

“Support is growing for building a large bank of iPSCs that scientists around the world can access,” says Zambidis, although large resources and intense quality-control would be needed for such a feat. However, Japanese scientists led by stem-cell pioneer Shinya Yamanaka are doing exactly that, he says, creating a bank of stem cells derived from cord-blood samples from Japanese blood banks.