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| Christine Grandizio |
Through the biobanks in our care, we offer a growing range of biosamples and products to scientists around the world. In the beginning, these collections were comprised of fibroblasts, lymphoblastoid cell lines, and DNA , but at Coriell we’ve expanded to include another useful research tool — the induced pluripotent stem cell (or iPSC).
To meet the growing demand for iPSCs, Coriell has its own Stem Cell Lab, led by Christine Grandizio. Christine’s team tackles all things iPSC: They create these cells, grow them, and coax them into becoming various adult cell types, all under careful quality control policies.
To learn more about these cells and the work of her lab, Christine answered the questions below.
What is an induced pluripotent stem cell?
An induced pluripotent stem cell or iPSC is a type of stem cell that has been reprogrammed—or "turned back"—into a stem cell state. These cells are derived from adult somatic cells such as skin cells from a biopsy or skin punch or peripheral blood mononuclear cells (PBMCs) from a blood sample.
Induced pluripotent stem cells have very distinct properties which classify them as a stem cell. They have the capability to divide and renew for long periods of time, allowing them to remain in culture for long-term experiments. IPSCs must remain undifferentiated—or in an unspecialized state—until a researcher wants to specialize the cell line for downstream analysis.
Being a pluripotent cell means that they are capable of differentiating or giving rise to specialized cell types such as neuronal cells, cardiomyocytes, lung progenitor cells, and many more cell types.
Why are these stem cells so valuable for the research community?
Researchers are able to use induced pluripotent stem cells for a wide array of studies and purposes.
These cells can be used in understanding the pathophysiology of diseases, disease modeling, drug screening and drug toxicity testing, gene corrections, regenerative medicine, among many others. Induced pluripotent stem cells are capable of differentiating or being turned into almost any cell type in the body. Scientists can turn an iPSC line into brain cells to study Alzheimer's disease, heart cells to study drugs for heart disease, or pancreatic cells to study diabetes.
At Coriell, we are able to create differentiated 2D cell models as well as 3D models called organoids. Organoids can more closely mirror human development and the disease or organ system of interest.
Researchers are also able to use iPSC lines and gene editing technologies to correct mutations (or introduce mutations into control cell lines) to better understand the pathophysiology of a range of diseases. This field has the potential to allow researchers to better understand disease function in general or in gene specific diseases with the hope to find treatments or cures for these diseases.
How does your team turn a skin cell into one of these stem cells?
The technology to create iPSCs from adult somatic cells was discovered in 2006 by Dr. Shinya Yamanaka. He discovered that there are four specific genes required to bring a somatic cell back to the embryonic-like state. These genes encoding transcription factors (now called Yamanaka reprogramming factors) are used to create iPSCs. The reprogramming factors must be delivered into the cells using various methods such as plasmid vectors, viral vectors, or RNA molecules.
My team uses a method to transfect the cells with Sendai virus to create our iPSCs. This method is quite efficient and safe for research purposes and we have optimized all of our protocols to achieve the highest quality induced pluripotent stem cell lines.
Can you talk about the importance of quality control and Coriell’s QC procedures?
Coriell's stem cell lab only distributes the highest quality cell lines. Reproducibility of experiments is critical to researchers. To obtain reproducible results, the starting material must be of the highest quality with no contamination or mutations introduced to the cell lines. We ensure our iPSC lines are uncontaminated, have an identity match to the starting parent fibroblast or PBMC cell line, and are free of any unwanted genetic mutations.
We also ensure that the iPSC lines have maintained their "stem cell" properties of self-renewal for long periods, have remained in the unspecialized state, and have the potential to give rise to the specialized cell types.
What do you find most interesting about induced pluripotent stem cells?
The fact that a "simple" blood or skin donation can lead to the creation of a stem cell with such a wide array of uses and possibilities is amazing.
I find the use of patient-derived iPSC lines for personalized medicine to be extremely interesting. Not only can the cells be used to study disease including rare diseases, but they can help scientists and doctors target treatments for patients, test patient specific drug toxicity, and patient-specific disease modeling, development, and progression.
Because of Coriell's vast experience as a biobank, the highly skilled stem cell team is able to create cell lines from patients for use by researchers around the world.
What else would you like the community to know about Coriell's stem cell lab?
The Coriell Stem Cell Lab offers a wide array of disease-specific and apparently healthy control cell lines. We are working to increase the diversity with available diseases and healthy cells lines as well providing samples of varying age, sex, and race to more closely match human diversity in general.
We are also able to provide patient biological replicates from samples meaning that we can provide multiple clones (fully characterized and quality assured) from the same individual. This is important to understand the random biological variation that may occur from cell lines derived from the same individual as well as between individuals.
