Many non-scientists are familiar with embryonic stem cell research—the possibility of plucking undifferentiated cells from a few days’ old embryo to establish cell lines that can be turned into any cell type in the body.

Ten years ago, when Chris Mayhew, PhD, came to Cincinnati Children’s, his main focus was to facilitate access to embryonic stem cell technologies for other investigators here. But around that same time, researchers in Japan developed a Nobel Prize-winning method of acquiring undifferentiated human stem cells. They coaxed cells from blood or skin samples back into undifferentiated stem cells that could form more than 200 other cell types.

“The process tricks the cells into losing any memory of what they were and induces a sort of blank slate, a naïve status,” says Mayhew, Director of the Pluripotent Stem Cell Facility (PSCF).

These induced pluripotent stem cells (iPSCs) allow researchers to create patient-specific stem cell lines for research, and eventually, it is hoped, for transplantation. Importantly, studies that use these types of stem cells advance medical science while avoiding the ethical controversies surrounding embryonic stem cell work.

More than 120 labs, 40 disorders

Mayhew’s team regularly creates iPSCs for other researchers. They also teach investigators how to grow and use these important cells in their own labs. So far, more than 90 labs from Cincinnati Children’s and 35 at other institutions have used the PSCF’s services. The team has produced iPSCs from more than 200 patients, diagnosed with at least 40 different diseases, including fragile X syndrome, Crohn’s disease, hereditary pulmonary alveolar proteinosis, and Duchenne muscular dystrophy.

Mayhew’s team has been involved with breakthrough work led by James Wells, PhD, and colleagues who have developed human organoids that mimic functions of the intestine, colon, stomach and, most recently, the esophagus. The service also collaborates with Takanori Takebe, MD, who is converting iPSCs into hepatocytes to create liver organoids.

The immediate potential of this work: using lab-grown human tissue instead of animal models to study disease and potential treatments. The longer-term hope: using iPSCs to grow personalized transplanted organs.

Going beyond

With the advent of CRISPR-Cas9 technology—a gene editing process that acts like a pair of molecular scissors to cut and paste strands of DNA—researchers can do even more with iPSCs.

For example, CRISPR-Cas9 is being used to repair mutations or to block the function of specific genes in iPSCs, allowing investigators to study how these genes function and contribute to disease.

Researchers also are studying how to use customized iPSCs to help clinicians compare and select potential treatments, and to help other investigators discover new medications.

Someday, the process might allow people to be transplanted with cells, complex tissue segments, or even entire organs derived from gene-corrected stem cells to reverse disease.

“This is an incredibly exciting time. Several preliminary clinical trials testing iPSC-derived cells are already underway, although we’re very much at the beginning of this journey as a field,” Mayhew says.