Professor Sheng Ding, PhD at the Scripps Research Institute in San Diego, CA and team 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. This is a new technology platform that 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 online issue of Nature Cell Biology.
During development, embryonic-like stem cells multiply and transform themselves into more mature cell types through a process known as differentiation, producing all of the body's different cell types and tissues. Past the embryonic stage, however, the human body has limited capacity to generate new cells to replace ones that have been lost or damaged. Scientists have been trying to develop ways to "reprogram" adult human cells back to a more embryonic-like, or pluripotent, state, from which the cells are able to divide and then change into any of the body's cell types. Using these reprogramming techniques, scientists hope to someday be able to use a patient's own cells, for example skin cells, convert them into heart or brain cells, and then insert them back into the patient to repair damaged tissues. In 2006, Japanese scientists reported that they could reprogram mouse skin cells to become pluripotent simply by inserting a set of four genes into the cells.
Although the technology to generate these cells, dubbed induced pluripotent stem (iPS) cells, represents a major advance, there are some hurdles to overcome before it can be adapted to therapies. The iPS technique requires a long time to generate iPS cells and then differentiate them into tissue-specific functional cell types, and the iPS cells generated in this manner are not ideal. Specifically, the procedure requires about four weeks for scientists to create iPS cells from skin cells and the process is far from efficient, with only one cell out of thousands making the complete transformation. Furthermore, once scientists obtain iPS cells, the cells have to go through the tricky procedure of inducing the iPS cells to differentiate into desired types of cells, requiring an additional two to four weeks.
Further, the process of generating mature cells from iPS cells is not foolproof. When, for example, scientists induce iPS cells to become heart cells, the resulting cells are a mix of heart cells and some lingering iPS cells. Scientists are concerned that giving these new heart cells (along with the remaining pluripotent cells) to patients might be dangerous. When pluripotent cells are injected into mice, they cause cancer-like growths. Because of these concerns, Ding and colleagues decided to try to tweak the process by completely bypassing the iPS stage and going directly from one type of mature cell (a skin cell) to another (a heart cell).
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 turned off their activities just after a few days, before the cells had turned into iPS cells. Once the four genes were switched off, the scientists initiated a signal in the cells to make them turn into heart cells. In 11 days the skin cells were transformed into beating heart cells.
In addition to better understanding the basic biology of stem cells, the next step will be further modification of the technique to remove the need for inserting the four genes, which has been linked to the development of cancer. As a result, many scientists, including Ding, have been working on new techniques to develop iPS cells without use of these genes. That has proven difficult. But with the new protocol that bypasses the iPS cell stage, the genes are needed for a much shorter time, and further refinement of the technique is likely to emerge quickly.