January 31, 2011
Skin To Heart Cells In Fewer Steps

Cutting weeks off the process Scripps scientists have found a faster way to convert adult skin cells into heart cells.

LA JOLLA, CA Scripps Research Institute scientists have converted adult skin cells directly into beating heart cells efficiently without having to first go through the laborious process of generating embryonic-like stem cells. The powerful general technology platform could lead to new treatments for a range of diseases and injuries involving cell loss or damage, such as heart disease, Parkinson's, and Alzheimer's disease.

The work was published January 30, 2011, in an advance, online issue of Nature Cell Biology.

"This work represents a new paradigm in stem cell reprogramming," said Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study. "We hope it helps overcome major safety and other technical hurdles currently associated with some types of stem cell therapies."

Think of a cell as a really complex state machine that is hard to manipulate. A large fraction of the challenge of producing cell therapies for our bodies amounts to finding ways to easily shift cells into desired states. Need heart muscle cells? That means you need a way to tell other cells to become heart muscle cells. You'll also need ways to get these cells to arrange themselves 3 dimensionally at the right locations to augment diseased failing heart cells. Tissue engineering techniques are needed to create those 3 dimensional arrangements are needed both in the body (to guide cells to repair existing organs) and outside of the body (to grow up new organs for transplant).

These researchers pulsed the cells with implanted genes for a much shorter period of time than previous techniques have used.

The team introduced the same four genes initially used to make iPS cells into adult skin fibroblast cells, but instead of letting the genes be continuously active in cells for several weeks, they switched off their activities just after a few days, long before the cells had turned into iPS cells. Once the four genes were switched off, the scientists gave a signal to the cells to make them turn into heart cells.

"In 11 days, we went from skin cells to beating heart cells in a dish," said Ding. "It was phenomenal to see."

I wonder about the effects of the short time scale. One problem with quickly turning an adult cell type into another adult cell type is that the some of the state information of the original cell type might linger. Methylation patterns that govern gene expression probably haven't all gotten updated into the new cell type (their epigenetic state has memory of the previous cell type) in such a short period of time. I suspect we need many more and better techniques for changing cell state that do so more thoroughly.

The science (or biotechnology) for creating induced pluripotent stem cells (iPS cells above) is moving along with better techniques every year. Back in August 2006 Shinya Yamanaka at Kyoto University in Japan first showed that the 4 genes Oct3/4, Sox2, c-Myc, and Klf4 could be used to induce pluripotency in adult cells. Basically, these genes caused cells to turn back into a more embryonic-like state. There is risk of producing cancerous cells from these attempts. But safer and safer ways to induce pluripotency keep getting published.

There's an overlap between cancer research and stem cell research because they both involve cell state and control of cell growth. Stem cell researchers need to avoid producing cancerous cells. Cancer researchers need to either kill cancer cells or tell them to shift into states which where they will stop growing or even kill themselves.

Share |      Randall Parker, 2011 January 31 11:00 PM  Biotech Stem Cells

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