CINCINNATI—Reprogramming mature human cells so they can become any cell type in the body is a key focus of the new Pluripotent Stem Cell Facility at Cincinnati Children’s Hospital Medical Center.
Known as “induced pluripotent stem cells” (iPSCs), they give researchers at Cincinnati Children’s and the University of Cincinnati (UC) College of Medicine powerful new tools to study what causes diseases and to grow genetically identical, patient-specific replacement tissues for future therapies, said James Wells, PhD, facility director and a researcher in the division of developmental biology at Cincinnati Children’s.
“This technology is a bit like the internal combustion engine in terms of how it will drive future advances in stem cell biology,” Wells says. “It allows us to use cells from patients to study what goes wrong at the genetic and cellular level to cause their disease—whether it’s muscular dystrophy, diabetes or any number of degenerative diseases. This technology could allow us to fix genetic defects and use these cells to generate healthy cells and tissues to treat or cure the patient.”
Pluripotent means the stem cells have the theoretical ability to become any of the more than 200 different cell types found in the human body. They provide a renewable source of cells for research into the emerging area of regenerative medicine. Regenerative medicine focuses on replacement therapies to create living, functional tissues that repair and replace tissues or organ function lost from age, disease, injury or congenital defects.
Because iPSCs come from, and are therefore genetically identical to the patient, they also should be safe in transplantation-based therapies without fear of rejection, Wells says. Using iPSCs from patients also does not come with the ethical concerns that surround stem cells derived from embryos.
The stem cell facility is a central source of human pluripotent stem cell technologies for researchers at Cincinnati Children’s, UC and elsewhere, Wells says. The facility provides training in the generation and use of pluripotent stem cells. It also is believed to be the only facility of its type in Ohio, Kentucky and Indiana, and one of only a relatively small number in the country.
“This type of stem cell technology is very expensive and time consuming for individual laboratories to establish and maintain. Relatively few institutions are in a position to make this commitment,” Wells explains.
“By making these cells available and bringing this technology to our institution, our goal is to help researchers ask new questions about the diseases they study, and hopefully find new therapies.”
To generate induced pluripotent stem cells, researchers take skin biopsies from healthy people or patients with specific diseases and grow the skin cells in a petri dish. Scientists begin the reprogramming process by inserting specific genes into a cell’s nucleus, instructing the mature cells to essentially reverse their life cycle and become unspecialized “embryonic-like” cells. It takes two to three months in a petri dish to make a single batch of iPSCs, says Chris Mayhew, PhD, co-director of the facility.
Using a patient’s own cells as a starting point, researchers can use iPSC technology to recreate and study disease progression in a petri dish. For example, starting with iPSCs from a patient with congenital blindness, scientists can study how specific genetic flaws cause abnormal development of eye cells. This gives researchers a first-ever opportunity to study the causes of a disease directly in the affected cell types and identify potential treatments.
Studying the onset of disease in human cells had not been possible before iPSC technology because genetic mistakes have already occurred in people by the time they become ill, Wells explains. Induced stem cells allow researchers to basically set back the developmental clock to square one and then move it forward again, he adds.
“Given the rapidly developing pace of this technology, it’s easy to envision a day where pediatric hospitals like Cincinnati Children’s will be able to provide services for generating and banking pluripotent stem cells from specific patients for future therapeutic use,” Wells says.
Cincinnati Children’s has so far invested about $600,000 through 2010 to open the facility. It now occupies 650 square feet of space. The medical center is discussing plans for significant expansion as demand for iPSCs, hESCs (human embryonic stem cells) and related services is expected to grow quickly, Wells says. The facility offers a full range of pluripotent stem cell services, including access to human pluripotent stem cell lines, generating iPSC lines, cell line maintenance, and training for scientists wanting to use cell lines in their own laboratories. Additional information about the facility, including applicable fees, is available at http://research.cchmc.org/stemcell.
Even as the medical center expands its work with induced pluripotent stem cells, continued research with human embryonic stem cells remains vital, in part because it serves as a comparison benchmark to ensure induced stem cells behave and function properly, Wells says.
The pluripotent stem cell facility is part of Cincinnati Children’s focus on translational research, where studies emphasize using new discoveries and technologies from the laboratory to stimulate development of pre-clinical and human clinical trials for new treatments.