Stem Cells: Using RNA to reprogram adult cells

To get around the problems of developing stem cells from embryonic material (problems mostly associated with ethical and religious considerations), biologists are researching a number of ways to produce stem cells from adult cells. Keep in mind that adult cells, for example skin or muscle cells, have already ‘set’ their form and function. Returning them to an undifferentiated state, a stem cell, is not easy. One approach has been to re-program the DNA of the adult cells, so when they reproduce the altered DNA reverts the cell to what is called an induced Pluripotent Stem Cell (iPSC). A pluripotent stem cell can, in turn, be converted into almost any form of adult cell. The problem is that altering the DNA carries certain risks, especially the risk of causing a mutation – a frequent source of cancer development.

Another approach taken by some labs is to use RNA (ribonucleic acid) as the medium for reprogramming adult cells. In a study published September 30, 2010 in the journal Cell: Stem Cell [Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA] Dr. Derrick J. Rossi (Harvard Medical School, USA) and team created synthetic RNA, which they call modifiedRNA, that encodes the creation of the appropriate proteins to produce stem cells (iPSCs).

This method has several advantages, not the least of which is that it doesn’t alter the DNA of the cell. This greatly reduces the risk of problems with mutation. Another advantage is found when the stem cells are applied to patient-specific therapy, such as the regeneration of certain kinds of tissue. Again, using a modified RNA, the stem cell can very efficiently be reprogrammed into a specific type of adult cell.

It is the efficiency of this approach that surprised the researchers:

Repeated administration of the modified RNAs resulted in robust expression of the reprogramming proteins in mature skin cells that were then converted to iPSCs with startling efficiency.

“We weren’t really expecting the modified RNAs to work so effectively, but the reprogramming efficiencies we observed with our approach were very high,” says Dr. Rossi.

[Source: Cell News]

The reprogramming of cells via modified RNA is promising, but still at a very early stage of development. As with all stem cell research, there are many steps between proof of concept and the approved application in human beings. Many questions must be answered, such as: How robust are stem cells produced in this way? Are there any complications? Is it practical to re-administer RNA continuously?

Relevant previous SciTechStory posts:
Induced stem cells not such good news
New method: Creating stem cells from fat cells

Research Spectrum

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