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Cellular Dynamics International reprograms blood cells into stem cells using a small volume of human blood
MADISON, Wis.—Cellular Dynamics International Inc. (CDI) has announced that its researchers have generated pluripotent stem cells, which have the ability to generate all tissue types in the body, from very small volumes of ordinary human blood samples. This significant provides a readily obtainable source of pluripotent stem cells from the millions of samples in storage at blood repositories and healthcare institutions worldwide. CDI is the first company to say it can make stem cells from something as readily available, and so representative of human diversity, as blood.
"Industry's challenge was to reliably create iPS cells from a commonly available and easily accessible tissue source and we focused on stored human peripheral blood samples," says Chris Kendrick-Parker, chief commercial officer of CDI. "Generating pluripotent stem cells from small volumes of blood, either freshly collected from a patient or accessed from blood storage repositories, provides a convenient source for generating patient-specific stem cells that are valuable research tools and may one day be used as a cellular therapy to treat disease."
According to Emile Nuwaysir, CDI's chief operations officer, the breakthrough allows researchers to use existing banked blood samples and standard procedures utilized in clinical trials to derive iPS cells.
"Utilizing standard tissue repositories and protocols make iPS cell technology easier to employ in clinical development as well as leverages banked samples, where going back to the individual or patient would be impossible," Nuwaysir says. "In addition, this new method will dramatically expand the utility of iPS cell technology by making it more accessible. Fifty years of intensive biomedical research has demonstrated that there is no single definition of human biology."
Nuwaysir points out that we are all individuals with different risk factors and predispositions to disease.
"In order to properly represent 'human' biology, our research models need to represent this diversity," he says. "iPS cell technology allows you to represent the diversity of human biology in an in vitro test by making individualized pluripotent stem cells from anyone. Previous methods to derive iPS cells required that the patient donate a skin biopsy to obtain the necessary tissue sample."
Nuwaysir points out that this is "the first step in paving the way for large-scale processing and industrialization of iPS cells."
To generate the induced pluripotent stem (iPS) cells, CDI scientists isolated T-cells, a type of white blood cell, from a 3 ml donor blood sample. The cells were stimulated, expanded and exposed to documented reprogramming factors. iPS cell colonies were observed after three weeks. Analysis revealed that the iPS cells are functionally identical to embryonic stem cells and iPS cells generated from other human tissue sources, that they carry the same genetic background as the source blood sample, and that they have the pluripotent ability to differentiate into any cell type.
Kendrick-Parker says this method now can be "employed in clinical development, as well as be added to existing genetic analysis sample banks as a way of establishing starting materials to understand individual biology without the need to start with materials like a skin punch or even a hair follicle."
Moving forward, Nuwaysir says CDI's next step will be to continue to perfect the iPS process and industrialize it.
"In addition, we will need to compare to other tissues of origin to make sure that this starting material (blood) will demonstrate the full pluripotency of other tissues that had previously been utilized for iPS generation," Nuwaysir points out.
Kendrick-Parker also adds that it is CDI's intention to engage its pharma partners to determine how this method can aid in better understanding of individual response to drugs in a clinical setting.
"We are engaged with many different groups to make large-scale panels of pluripotent stem cell lines for use in basic research, drug discovery and development, and drug toxicity testing," he says. "These panels will better represent the basic diversity of human biology and are better model systems for scientists to study human biology."
CDI was formed in 2004 by stem cell pioneer James Thomson and three other University of Wisconsin researchers. The company has 65 employees and finished ramping up its stem cell production facility in June, says Bob Palay, the Madison biotech company's chairman and chief executive. Cellular Dynamics has sales in the "multimillions" of dollars, he said.
CDI also announced recently that it expanded its drug development testing agreement with Roche so that it will be supplying the drug industry giant with more iPS heart cells and other types of cells over the next two years. The companies also will collaborate to perform various tests on the cells.
Under this agreement, CDI will supply purified cardiomyocytes, created from induced iPSCs, to Roche, and the two companies will collaborate to perform various cell characterization, toxicological, and electrophysiological response experiments. The agreement also includes an ongoing cardiomyocyte supply contract post collaboration.
Embarked upon originally in March 2008 as a validation of CDI's human pluripotent stem cell technology, the expanded agreement is a testament to the success of the first phase. This next phase moves the companies toward assessing iPSC-derived cardiomyocytes as a cardiovascular safety pharmacology as well as toxicology tool.