April 26, 2009
Cells Made Pluripotent With Injected Proteins

We need the ability to turn our own adult cells into pluripotent (i.e. capable of becoming all cell types) stem cells. Stem cells made from our own tissue will be immunologically compatible and not rejected. Such stem cells will serve as a useful starting point to grow replacement organs and to create cell therapies. The first methods developed for converting adult cells into stem cells used gene therapy that runs the risk of converting cells into cancers. But a number of labs have developed successively safer ways to make pluripotent stem cells from adult cellls. Finally a team at Scripps has found a way to totally avoid the need for gene therapy. In their very promising approach the scientists used proteins made from the genes that cause cells to become pluripotent.

In a paper publishing online April 23rd in Cell Stem Cell, a Cell Press journal, Dr. Sheng Ding and colleagues from the Scripps Research Institute in La Jolla, California, report an important step forward in the race to make reprogrammed stem cells that may be better suited for use in clinical settings.

Ding and his colleagues show that mouse cells can be reprogrammed to form stem cells with a combination of purified proteins and a chemical additive, thus avoiding the use of genetic material.

The discovery three years ago that adult cells could be reprogrammed to form induced pluripotent stem cells, or iPS cells, with similar properties to embryonic stem cells was a major scientific breakthrough. These cells hold enormous potential for drug development and even cell therapy processes, and this promise has garnered significant attention from scientists and the media worldwide. However, a major caveat to the eventual application of iPS cells is that until now all the methods used to generate them have required the introduction of genetic material to make the transcription factors needed for reprogramming. Although some research groups have recently generated iPS cells that lack genetic modifications, even the most advanced methods used genes in the form of plasmids, and thus the risk of genetic mutations caused by the introduced sequences remained.

In their new paper, Ding and co-authors avoid this risk entirely by adding specially modified versions of reprogramming proteins directly to the growing fibroblasts. The proteins are broken down by the cells after they are added to the culture, so to sustain protein activity long enough to induce reprogramming the authors used repeated cycles of protein addition. Ding and colleagues named the reprogrammed cells that arise from this process "protein-induced pluripotent stem cells," or piPS cells.

The Scientist has a good article on this advance (free registration required).

Although the technique was much less efficient than virus-based approaches -- 0.006% compared to 0.067% using Yamanaka's original method -- these reprogrammed cells, dubbed "protein-induced pluripotent stem cells," or piPS cells, passed all the benchmarks of pluripotency both in vitro and in vivo. Ding's team also showed that they could do away with one of the proteins, c-Myc, although this further reduced the already poor reprogramming efficiency by about a third.

Lots of labs will jump on this and work on ways to boost the conversion efficiency. One key to being able to do it at all came from Douglas Melton's lab at Harvard just last year. The Scientist reports a histone deacetylase inhibitor was needed in addition to the proteins. No doubt other compounds will be found that further boost the conversion process.

Being able to create pluripotent stem cells at will provides multiple benefits. The older approach of cloning with eggs doesn't just stir ethical objections from some Christians. That approach also requires availability of human eggs. Well, harvesting eggs from women entails risks and costs and not all women are willing to donate their eggs. The ability to avoid the generation of an embryo using eggs really helps make it a lot easier to create pluripotent stem cells from every person's own adult cells.

While a lot has been said about the importance of pluripotent stem cells they are, in a sense, just the starting point. Lots more work is needed to figure out how to turn them into all the other cell types that make up a human body. Each type of cell has a bunch of molecular switches (e.g. methyl groups attached to the DNA) that hold them in their state. We need to find ways to turn cells into each of the cell types. We also need to find ways to deliver the cells to where they are needed and to get them to attach and assume appropriate positions in the aged and damaged tissue. Our lives and eventual rejuvenation depend on rapid progress in solving this next set of problems.

Share |      Randall Parker, 2009 April 26 06:13 PM  Biotech Stem Cells


Comments
Pablo said at April 27, 2009 7:47 AM:

"The older approach of cloning with eggs doesn't just stir ethical objections from some Christians."

So, it's just a subset of Christians who have ethical objections to destroying cloned human beings for the sake of biomedical research? I would have guessed the universe of folks who object couldn't be so easily, and condescendingly, labeled.

Kent said at April 27, 2009 8:47 AM:

I wonder if they'll include this in Bioshock 2.

Kirk said at April 27, 2009 10:16 AM:

As a Parkinson's patient for the past 14 years, I can only urge these scientists to "go go go."

I do have a policy question to put out there, and I hope this is the right forum; if not, accept my apologies:
Do you think that the advances made in this field, including, but not limited to, the information in this article, were helped or hindered by George Bush's banning of testing on new embryonic cells in 2001?

I contend that they were helped, because the ban forced the human mind to come up with better alternatives (i.e., not as virulently cancer-causing)than embryonic cells. What do you think?

Please note that I'm a pro-choice layman. So I ask you to temper your condescension and/or your moral and ethical opinions.

LarryD said at April 27, 2009 11:50 AM:

Bush's actions in this regard have been widely misreported. Before Bush, there was no Federal funding of any kind for embryonic stem cells (ESC). Bush made funding available for ESC research as long as it used already established cell lines.

In retrospect, I think he shouldn't have bothered. Adult stem cell (ASC) research was where all the therapies and successes were coming from, even now, ESC has only promising techniques, no actual therapies. Once he made Federal funding available, lobbying began to loosen restrictions, the existing ESC cell lines were suddenly "discovered to be contaminated" (which rather renders questionable the basic competency of the responsible organization), and a lot of propaganda was produced which completely ignored the ASC research, touting ESC theoretical possibilities while ignoring the paucity of results.

Meanwhile ASC research just kept on trucking, including research into creating pluripotent cells from adult cells. So I think all the hullabaloo over ESC has been meaningless for actual R&D, and a waste of time and money for those involved.

Jasmine said at April 27, 2009 1:46 PM:

Bush helped to spur induced stem cell research by shunting some of the federal funding away from embryonic stem cell research. By putting the brakes somewhat on federally funded ESC research, Bush helped route funding to alternate stem cell sources.

But you have to really despise Bush for locating New Orleans in such a vulnerable geographic location back in 1722. The nerve of the man, and he sank the Titanic too!

Randall Parker said at April 27, 2009 7:05 PM:

Kirk,

Regards Bush's restrictions: Read stem cell researcher Evan Snyder's comments about this in 2003. We needed the ability to convert adult stem cells into embryonic cells without using eggs. So Bush's restrictions certainly increased the motive of scientists to solve that problem. Scientists are making very rapid progress toward that goal. Obama's lifting of the human embryonic stem cell restrictions strikes me as opening the door of the barn after the horses already found a way to jump thru a window.

Also, a lot of work needs to take place in mouse cells anyway because it is cheaper to work out solutions to problems in mice and other lab animals first.

LarryD,

We always needed pluripotent cells. Adult stem cells don't grow as fast and can't become as many types of cells. Even all pluripotent lines are not the same. They do not all grow fast. I'd like to know how fast these cells above grow once converted.

Pablo,

Grow a thicker skin. I wasn't trying for condescension. I tried rewording that line a few ways when I wrote the post. But I couldn't come up with a succinct better way to say it. Really the bulk of the opposition to human ESCs came from some (not all) Christians. I don't think the Muslims object to human ESC research. They still believe a quickening concept about fetal development that the Catholic Church has abandoned in some previous century (forget which one). Certainly the Mormons are fine with human ESC research. Haven't heard from Buddhists or Hindus or Zoroastrians on this subject.

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