"Industry's challenge was to reliably create iPS cells froma commonly available and easily accessible tissue source and we focused onstored human peripheral blood samples," says Chris Kendrick-Parker, chiefcommercial officer of CDI. "Generating pluripotent stem cells from smallvolumes of blood, either freshly collected from a patient or accessed fromblood storage repositories, provides a convenient source for generatingpatient-specific stem cells that are valuable research tools and may one day beused 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 andstandard procedures utilized in clinical trials to derive iPS cells.
"Utilizing standard tissue repositories and protocols makeiPS cell technology easier to employ in clinical development as well asleverages banked samples, where going back to the individual or patient wouldbe impossible," Nuwaysir says. "In addition, this new method will dramaticallyexpand the utility of iPS cell technology by making it more accessible. Fiftyyears of intensive biomedical research has demonstrated that there is no singledefinition of human biology."
Nuwaysir points out that we are all individuals withdifferent risk factors and predispositions to disease.
"In order to properly represent 'human' biology, ourresearch models need to represent this diversity," he says. "iPS celltechnology allows you to represent the diversity of human biology in an invitro test by making individualized pluripotent stem cells from anyone.Previous methods to derive iPS cells required that the patient donate a skinbiopsy to obtain the necessary tissue sample."
Nuwaysir points out that this is "the first step in pavingthe way for large-scale processing and industrialization of iPS cells."
To generate the induced pluripotent stem (iPS) cells, CDIscientists isolated T-cells, a type of white blood cell, from a 3 ml donorblood sample. The cells were stimulated, expanded and exposed to documentedreprogramming factors. iPS cell colonies were observed after three weeks.Analysis revealed that the iPS cells are functionally identical to embryonicstem cells and iPS cells generated from other human tissue sources, that theycarry the same genetic background as the source blood sample, and that theyhave the pluripotent ability to differentiate into any cell type.
Kendrick-Parker says this method now can be "employed inclinical development, as well as be added to existing genetic analysis samplebanks as a way of establishing starting materials to understand individualbiology without the need to start with materials like a skin punch or even ahair follicle."
Moving forward, Nuwaysir says CDI's next step will be tocontinue to perfect the iPS process and industrialize it.
"In addition, we will need to compare to other tissues oforigin to make sure that this starting material (blood) will demonstrate thefull pluripotency of other tissues that had previously been utilized for iPSgeneration," Nuwaysir points out.
Kendrick-Parker also adds that it is CDI's intention toengage its pharma partners to determine how this method can aid in betterunderstanding of individual response to drugs in a clinical setting.
"We are engaged with many different groups to makelarge-scale panels of pluripotent stem cell lines for use in basic research,drug discovery and development, and drug toxicity testing," he says. "Thesepanels will better represent the basic diversity of human biology and arebetter model systems for scientists to study human biology."
CDI was formed in 2004 by stem cell pioneer James Thomsonand three other University of Wisconsin researchers. The company has 65employees 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 drugdevelopment testing agreement with Roche so that it will be supplying the drugindustry giant with more iPS heart cells and other types of cells over the nexttwo years. The companies also will collaborate to perform various tests on thecells.
Under this agreement, CDI will supply purifiedcardiomyocytes, created from induced iPSCs, to Roche, and the two companieswill collaborate to perform various cell characterization, toxicological, andelectrophysiological response experiments. The agreement also includes anongoing cardiomyocyte supply contract post collaboration.
Embarked upon originally in March 2008 as a validation ofCDI's human pluripotent stem cell technology, the expanded agreement is atestament to the success of the first phase. This next phase moves the companiestoward assessing iPSC-derived cardiomyocytes as a cardiovascular safetypharmacology as well as toxicology tool.