In celebration of CIRM’s 20th anniversary, we have been reflecting on some of the early projects we supported and their outcomes. This blog is a little different, because it also marks the end of a project.

In 2013 CIRM announced a $32 million project to create a repository of stem cell lines from people with common complex diseases such as Alzheimer’s disease, heart disease, liver disease, and neurodevelopmental disorders (as well as some people without diseases). At the time, a fairly new technology allowed researchers to create or “induce” stem cells out of human tissues like skin or blood. These are known as induced pluripotent stem cells or iPSCs.

Because the technology was so new, the effort of identifying donors, collecting tissues, and creating the iPSCs was more work than most research groups could take on. The hope was that by supporting the creation of iPSCs from people with common diseases CIRM could accelerate research into better understanding and perhaps developing ways of treating these conditions. The first cell lines were available to researchers in 2015.

A key aspect of CIRM’s iPSC bank is that cells came from a wide range of individuals. That’s because many common diseases are complex and arise through a range of different genetic and environmental factors, each of which has a small effect on how the disease develops and progresses. By using a large number of cells, each with different genetic variations, the goal was for scientists to be able to study these complex diseases and their possible cures. Also, genetic information is available for the cell lines, so if scientists find that a group of cells respond well to a particular treatment, for example, or show side effects from a new drug, they can identify genetic commonalities and use that information to identify who might benefit from a therapy or be at risk of side effects.

A powerful research tool

Fast forward to 2025 and the cell lines have been distributed to 128 institutions in 22 US states and 21 countries, supporting research across the globe. A comprehensive analysis of outcomes has not been performed, but some published research outcomes include:

• One study, using more than 100 CIRM iPSC lines, identified a gene that may be responsible for why some human fetuses are more susceptible to the Zika virus. This may help explain why some prenatal Zika virus infections resulted in devasting effects on brain development but others did not, and could help identify possible therapies. 
  
• Several studies looked at CIRM iPSC lines from people with a liver disease (non-alcoholic fatty liver disease, NAFLD) to better understand its underlying causes. One study, using 7 iPSC lines, and another, using 37 lines, showed that liver cells made from people with NAFLD accumulated much more fat than those from control iPSC, just like in the disease. Another group used this NAFLD model in a dish to find that fat accumulating in liver cells was not related to insulin resistance in people with Type 2 diabetes.
  
• A gene variant called APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer’s disease but individuals with the APOE3 variant also get the disease, just fewer of them. One study using several CIRM iPSC lines was able to show similarities and differences between brain-like structures made from Alzheimer’s disease patient iPSCs that were either APOE4 or APOE3. Both types showed similar increases in amounts of a protein called amyloid beta, which is a hallmark of people with Alzheimer’s disease, when compared to healthy controls. Interestingly, though, brain-like structures from patients with the APOE4 gene variant showed more cell death, more loss of connections between neurons, and more accumulation of a protein called p-tau, compared to brain-like structures from patients with the APOE3 variant. Experiments in which APOE4 was genetically converted to APOE3 in the iPSC led to further insights in the role of APOE4 in Alzheimer’s disease. These kinds of studies can help identify how APOE4 increases the risk of the disease and suggest possible therapies. 
  
• One large-scale study used almost 300 CIRM iPSC lines to determine how genetic variation influences the shape and distribution of cellular structures, like the nucleus (where DNA resides), plasma membrane (outer membrane of cells), mitochondria (powerhouses of cells), and others within undifferentiated iPSCs. Using robotics, cutting edge microscopy and image analysis techniques, they were able to identify associations between certain genetic variants and features like asymmetries in the distribution of mitochondria, size of RNA particles, and spatial distribution of a cellular organelle called endoplasmatic reticulum. The genetic variants the study identified are known to contribute to cancer development or developmental disorders, providing new insights that could be relevant for developing future therapies. 

Looking to the future

Sadly, all good things must come to an end, and that time is now for the iPSC bank as CIRM recently announced. Because of changes in how the repository was being maintained, keeping it going would cost CIRM about $400,000 initially then about $300,000 per year ongoing. This annual cost is above what comes in through sales of the cell lines and diverts funds away from other critical investments. There are also now other iPSC repositories where researchers can get cell lines.

A cell storage facility will be storing a few vials of cells for each iPSC line, without further distribution, allowing the repository to be revived should that be warranted by future interest and circumstances. What’s more, since iPSC lines can be propagated in the laboratory indefinitely, those CIRM lines distributed over the last 9.5 years can continue to yield new information about human biology and disease in the laboratories that acquired them and their collaborators.

We are both proud of the research that has come out of the bank and sad to see it end. This is just one of many ways over the years that CIRM has helped scientists overcome barriers to research and move discoveries toward cures, and we look forward to doing more of the same in the future guided by our recently announced Strategic Allocation Framework that prioritizes our resources to maximize impact.

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Written by guest contributor Amy Adams