Scientists at UCLA Reprogram Human Skin Cells into Embryonic Stem Cells

UCLA stem cell scientists have reprogrammed human skin cells into cells with the same unlimited properties as embryonic stem cells, without using embryos or eggs.

Led by scientists Kathrin Plath and William Lowry, UCLA researchers used genetic alteration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, which have the ability to become every cell type found in the human body. Four regulator genes were used to create the cells, which are called induced pluripotent stem cells, or iPS cells.

The UCLA study confirms the work of researchers Shinya Yamanaka at Kyoto University and James Thomson at the University of Wisconsin, first reported in late November 2007. The UCLA research appears today in an early online edition of the journal Proceedings of the National Academy of the Sciences.

The implications for disease treatment could be significant. Reprogramming adult stem cells into embryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine.

A patient's skin cells, for example, could be reprogrammed into embryonic stem cells, and those stem cells could be prodded into becoming various cells types — beta islet cells to treat diabetes, hematopoetic cells to create a new blood supply for a leukemia patient or motor neuron cells to treat Parkinson's disease.

"Our reprogrammed human skin cells were virtually indistinguishable from human embryonic stem cells," said lead author Plath, an assistant professor of biological chemistry and a researcher with UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

"Our findings are an important step towards manipulating differentiated human cells to generate an unlimited supply of patient-specific pluripotent stem cells. We are very excited about the potential implications,” Plath added.

The UCLA work was completed at about the same time the Yamanaka and Thomson reports were published. Taken together, the studies demonstrate that human iPS cells can be easily created by different laboratories and are likely to mark a milestone in stem cell-based regenerative medicine, Plath said.

These new techniques to develop stem cells could potentially replace a controversial cell-reprogramming method known as somatic cell nuclear transfer (SCNT), which is sometimes referred to as therapeutic cloning. To date, therapeutic cloning has not been successful in humans.

However, top stem cell scientists worldwide stress that further research comparing these reprogrammed iPS cells with stem cells derived from embryos — considered the gold standard — is necessary. Additionally, many technical problems, such as the use of viruses to deliver the four genes for reprogramming, need to be overcome to produce safe iPS cells that can be used in the clinic.

"Reprogramming normal human cells into cells with identical properties to those in embryonic stem cells without SCNT may have important therapeutic ramifications and provide us with another valuable method to develop human stem cell lines," said first author Lowry, an assistant professor of molecular, cell and developmental biology and a Broad Stem Cell Center researcher. "It is important to remember that our research does not eliminate the need for embryo-based human embryonic stem cell research but rather provides another avenue of worthwhile investigation."

The four genes used in combination to reprogram the skin cells regulate expression of downstream genes and either activate or silence their expression. The reprogrammed cells were not just functionally identical to human embryonic stem cells - they also had an identical biological structure, expressed the same genes and could be coaxed into giving rise to the same types of cells.