Induced Pluripotent Stem (iPS) Cells

induced-pluripotent-stem-cells“We are making the human body available for research.” -Emile Nuwaysir Cellular Dynamics

While the lack of funding hindered stem cell research, scientists sought out alternatives to study disease at the cellular level. In 2006, Dr. Shinya Yamanaka of Kyoto University took skin cells from a mouse and exposed them to various combinations of 30 genes known to be important in cellular development. When Dr. Yamanaka discovered the right combination of four genes, he harnessed the natural capability of viruses to enter cells and used them as vehicles to deliver these four genes into the cell’s genome. Once they entered the genome, the genes reprogrammed the skin cells into an embryo-like state.

In 2007, Dr. Yamanaka used the same four factors to turn the clock back on human skin cells. That same year, Dr. James A. Thomson of the University of Wisconsin also created these powerful human stem cells – but through a different combination of genes. This new type of stem cell, called an induced pluripotent stem (iPS) cell (or iPSC), promises to revolutionize the way human disease is studied. Drs. Thomson and Yamanaka went on to share the 2011 King Faisal International Prize in Medicine for their pioneering work. A year later, Dr. Yamanaka and Sir John B. Gurdon, a British biologist who utilized frog eggs in 1962 to determine that cells posses this reversible property, were awarded the Nobel Prize for Medicine and recognized as the visionaries behind iPSC technology.

Michael Christman on “disease in a dish” technology:
“Screening drug candidates in a stem cell model will likely result in effective drugs getting into the market faster, since testing in the diseased environment has been proven even prior to the clinical trial. Significantly, this technology has the potential to offer medicines that are better targeted for individual patients. Finally, it also promises to reduce the cost burden of research and development, and in turn, the cost to patients for their prescription drugs.”

Next Generation iPS Cells

Inserting virus DNA that combines with a cell’s DNA can trigger that cell to become cancerous. Due to this undesirable outcome, scientists are moving away from using viruses and have found a new approach to reprogram cells using more benign vehicles to deliver the genes. One such technique involves circular DNA called plasmids. Plasmids are DNA molecules that are separate from, and can replicate independently of, the chromosomal DNA; they are designed to stay separate from the host cell’s genome.

In the lab, scientists introduce two or three plasmids containing multiple reprogramming genes, into the cells. The plasmids reprogram the cells into a stem cell state without integrating into the genome themselves. For example, when researchers transfer the circular DNA into blood cells, the introduced genes turn on, converting the blood cells into the desirable induced pluripotent stem cells within just 14 days. Unlike viral methods, after the iPS cells are formed, the circular DNA delivered into the blood cells is gradually lost.