天博体育

Embryonic stem cell research听continues to be听a political and听 hot potato听that stirs up a lot of emotion and听argument.

In the meantime, researchers are making some remarkable progress using听an alternative stem cell approach called induced pluripotent听stem cells, or iPSCs (sometimes that gets听 shortened to iPS).

An induced pluripotent stem cell is听an adult cell, often a skin cell, that has been 鈥渞eprogrammed鈥� so it听takes on the pluripotent properties of an embryonic cell. Pluripotency in this context means the capacity for a cell to听generate cells of all different types. If a cell is pluripotent, it can give rise to blood cells, heart cells, kidney cells, brain cells鈥攜ou name it.

Researchers at the are reporting听in tomorrow鈥檚听The New England Journal of Medicine (NEJM) that they have generated working听heart muscle cells鈥攃ardiomyocytes鈥攆rom human skin cells using iPSCs. That鈥檚听quite a feat, but the German research team听acknowledge that it has been done before (stem cell research is competitive, so firsts are important).

Their听innovation was producing听functional听cardiomyocytes from people听with an听inherited condition鈥攊n this case听, which听can lead to potentially fatal heart arrhythmias.

The heart cells their experiments听produced听had听the genes that cause听long-QT syndrome type 1.听Moreover, they听behaved like long-QT type 1听cardiomyocytes. When stimulated, they showed the same kind of abnormal electrical activity.听They also responded to a propranolol, a beta blocker, in the same way听鈥渞eal鈥澨齝ardiomyocytes from a long-QT syndrome type 1 patient would.

Obviously you wouldn鈥檛 use听these flawed cells to fix the heart of someone with the disease.听But having听iPSC-generated human听cells听that are specific to a patient听and a particular condition could听prove to be an ideal听testing ground for research and drug development.听

, a cardiovascular researcher at the Harvard Stem Cell Institute and Harvard-affiliated Beth Israel Deaconess Medical Center,听 wrote an editorial about this study that was published in听same issue of NEJM. This is how he put it:

Although much excitement has been generated by the potential for therapeutic delivery of such cells [iPSCs]听for tissue regeneration, considerable challenges remain to make this a practical reality. A more immediate application of this technology that may also have important implications for human health lies in the development of cellular models for disease genetically matched to specific patients. Such models provide a human context for unraveling disease pathophysiology, validating therapeutic targets, and examining the response to pharmacologic interventions.

The听German researchers used a retrovirus to carry four genes into听the skin cells to turn them into iPSCs.听 That is now the tried and true method for making iPSCs, but听using听retroviruses听to reprogram cells raises legitimate concerns about retroviral听DNA听getting into the host cell鈥檚 genome and听possibly having听cancerous and other harmful effects.

, a Harvard Stem Cell Institute researcher, has used adenoviruses, which cause the common cold, to听ferry genes into cells and create iPSCs. Adenoviruses don鈥檛 insert themselves into the genome of听host cells, so they would presumably be safer than retroviruses.

And just听last week, another Harvard researcher, , reported that his research group had successfully听reprogramned human skin cells into iPSCs using听RNA,听avoiding the use of viruses altogether.

Does all this progress with听iPSCs mean there鈥檚 no longer a need听for embyonic stem cell research? It鈥檚 a question freighted with听political as well as scientific and medical听significance.

鈥淣o鈥澨� is听the emphatic answer from the overwhelming听majority of stem cell researchers. The prevailing opinion in the field听is that even if all the concerns about viral DNA and how pluripotent cells are generated were assuaged, there are听still听unresolved questions about whether iPSCs can ever be as听pluripotent as听the stem cells that come from听embryos. After all, embryonic stem cells are, in a sense, naturally pluripotent and don鈥檛 have to be induced into a primordial stem state.听听

There鈥檚 some reason to believe that听the cells that听iPSCs听come听from may听imprint them听in some way that sets听limits on听the cells they鈥檙e听 able to generate.听Perhaps iPSCs听can generate some cells, not others, or there are flaws in the cells they do produce.

In an interview yesterday,听Hochedlinger pointed to听earlier this year that show听certain important 鈥済ene clusters鈥� are inactive in听听iPSCs but听 not in embryonic stem cells (although there do seem to be ways that the iPSC gene clusters could听be activated).

Here is听a relevant excerpt from a听profile of , director of听the National Institutes of Health, in the September 6, 2010, issue of The New Yorker magazine (the Thomson-Yamanaka breakthrough is a reference to听iPSCs):

When I asked Collins about the Thomson-Yamanaka breakthrough听he said that not enough was yet known about such cells to guess whether they have the same therapeutic potential as embryonic stem cells. For example, scientists have learned that the pluripotent cells derived from adult tissues retain some memory of that tissue. 鈥淲ill that matter for the therapeutic uses we all dream of?鈥� he asked. 鈥淣o one knows, but it would be foolish now to proceed without comparing them at every step to the gold standard for pluripotency鈥攁nd that remains the human embryonic stem cell. So it鈥檚 not 鈥榚ither/or鈥� that we should be pursuing. It鈥檚 鈥榖oth/and.鈥� 鈥�