Frequently Asked Questions About Stem Cell Science

Induced pluripotent stem cells
Induced pluripotent stem cells reprogrammed from normal adult human tissue and have not yet been differentiated, but remain in the pluripotent state. Image by Matt Spindler/Gladstone Institutes

Here are answers to frequently asked questions about induced pluripotent stem cells, or iPS cells, the type of cell that has been reprogrammed from an adult cell, such as a skin or blood cell.

What are induced pluripotent stem cells?

Induced pluripotent stem cells, or iPS cells, are a type of cell that has been reprogrammed from an adult cell, such as a skin or blood cell. iPS cells are pluripotent cells because, like embryonic stem cells, they can develop into virtually any type of cell. iPS cells are distinct from embryonic stem cells, however, because they are derived from adult tissue, rather than from embryos. iPS cells are also distinct from adult stem cells, which naturally occur – in small numbers – in the human body.

In 2006, Shinya Yamanaka developed the method for inducing skin cells from mice into becoming like pluripotent stem cells and called them iPS cells. In 2007, Yamanaka did the same with adult human skin cells.

Shinya Yamanaka
Shinya Yamanaka, MD, PhD

Yamanaka’s experiments revealed that adult skin cells, when treated with four pieces of DNA (now called the Yamanaka factors), can induce skin cells to revert back to their pluripotent state. His discovery has since led to a variety of methods for reprogramming adult cells into stem cells that can become virtually any cell type – such as a beating heart cell or a neuron that can transmit chemical signals in the brain. This allows researchers to create patient-specific cell lines that can be studied and used in everything from drug therapies to regenerative medicine.

How are iPS cells different from embryonic stem cells?

iPS cells are a promising alternative to embryonic stem cells. Embryonic stem cells hold tremendous potential for regenerative medicine, in which damaged organs and tissues could be replaced or repaired. But the use of embryonic stem cells has long been controversial. iPS cells hold the same sort of promise but avoid controversy because they do not require the destruction of human embryos. Nor do they require the harvesting of adult stem cells. Rather, they simply require a small tissue sample from a living human.

Why is iPS cell technology so important?

In addition to avoiding the controversial use of embryonic stem cells, iPS cell technology also represents an entirely new platform for fundamental studies of human disease. Rather than using models made in yeast, flies or mice for disease research, iPS cell technology allows human stem cells to be created from patients with a specific disease. As a result, the iPS cells contain a complete set of the genes that resulted in that disease – and thus represent the potential of a far–superior human model for studying disease and testing new drugs and treatments. In the future, iPS cells could be used in a Petri dish to test both drug safety and efficacy for an individual patient.

What has happened since Shinya Yamanaka developed iPS technology?

There have been several advancements in the field since Yamanaka first developed iPS cell technology. The most recent advancement is called direct reprogramming, which offers a host of advantages when adult cells are reprogrammed into another type of cell without having to revert back to the pluripotent state.

Deepak Srivastava
Deepak Srivastava, MD

Deepak Srivastava, MD, a UCSF professor in the departments of pediatrics and biochemistry and biophysics, who directs cardiovascular research at the Gladstone, earlier this year announced the direct reprogramming of cardiac fibroblasts – the heart’s connective tissue – directly into beating cardiac-muscle cells in animal animal hearts while Steve Finkbeiner, a senior investigator at the Gladstone, MD, PhD, announced the creation of a human model of Huntington's disease, based on reprogrammed skin cells of patients with the disease.

Also this year, Yadong Huang, MD, PhD, an associate investigator at the Gladstone, announced the use of a single genetic factor to reprogram skin cells into cells that develop on their own into an interconnected, functional network of brain cells.

How can iPS cell technology be used in the future?

1. Regenerative medicine. Gladstone scientists are testing the regenerative effects of iPS cells on animal models. For example, Deepak Srivastava, MD, a UCSF professor in the departments of pediatrics and biochemistry and biophysics and director of the Gladstone Institute of Cardiovascular Disease, is working on ways to use iPS cell technology to re-grow heart muscles in individuals who have suffered heart attacks. Researchers are also testing whether iPS cell technology can help individuals with spinal cord injuries, as well as neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s.

Bruce Conklin
Bruce Conklin, MD

2. Testing drug safety. Many drugs fail because they cause health problems that are not detected until clinical trials begin. Using iPS cell technology, Bruce Conklin, MD, a professor of medicine at UCSF and a senior investigator at the Gladstone Institute of Cardiovascular Disease, is developing heart cells from reengineered adult human cells to test toxicity of drug therapies earlier in the drug-development process — with the goal of reducing the cost and time required for expensive animal and human trials.

3. Personalized medicine. Drugs interact differently with different patients due to each individual’s unique genetic makeup. Using a patient’s own cells, researchers can leverage iPS technology to create brain, heart, liver and other cells with that patient’s DNA. Those cells could then be used to test potential drug interactions for that specific patient, or potentially for transplantation or regeneration.

Photo by Chris Goodfellow