adult stem cells, Bioethics, embryonic stem cells, induced Pluripotent Stem Cells, iPS, medical technology, regenerative medicine, reprogrammed cells, research, science, Yamanaka

>Translation of Yamanaka, Yu "induced Pluripotent Stem Cells" (Revised)

>Scientists who report their findings are expected to discuss the problems as well as the outcome of their research. This is usually found in the “Discussion,” “Conclusions” or “Results” section of the paper. This is the best place to figure out what the researches intended, what they did and what the report means. (Then you go back and check to see if they proved what they “discussed.” And then, you wait for other labs to confirm it.)

The actual (Takahashi et al., “Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,” Cell (2007).) Cell article on reprogrammed adult fibroblast skin cells, the “induced Pluripotent Stem Cells) or “iPS,” is available for free, here. The Science Magazine report about similar work by James Thomson from Wisconsin (the researcher who reported the production of human embryonic stem cells in the first place) is supposed to be published November 22, 2007. (Editorial note 11/30/07 – Science published the Thompson and Yu report the same day that Tamanaka’s report was published, two days ahead of schedule. See my “translation,” here.)

To the best of my understanding, here’s a translation into layman’s terms about what the Takahashi/Yamaka report means:

While it took a lot of cells and more time than the researchers first expected because the human iPS grew much slower than the mouse iPS,

1. The cells that grew looked and functioned like human embryonic stem cells with a few minor differences,
2. They believe they proved that their technique is responsible for all the new pluripotent cells that were found in their cultures(there weren’t any cells from another culture introduced accidentally or on purpose and which would make them look more successful than they were),
3. The cells could be directed to develop nerve cells and heart cells,
4. They were able to use several types of adult specialized cells to achieve iPS, and
5. The researchers suggest several possible ways to overcome the drawbacks of the process.

The authors believe that the inefficiency or the need to begin with lots of adult cells and wait a little longer for a substantial amount of human iPS should not be a “practical” problem because the adult cells are easy to obtain and labs all over the world should be able to reproduce their results. Since the technique should be well-funded (it qualifies for US Federal funding and is ethical, since no human beings have to die), the authors believe it will be possible for lots of researchers to work on them.

If I were to predict the future, I would anticipate banks of iPS – or even specialized or intermediate forms of cells that are produced from iPS – being stored for each of us, just in case. In the very long term, we will learn more about stimulating our on bodies’ stem cells from research on these cells, so that we can repair or prevent damage without transplants or waiting for cultures to grow in the lab.

The major hurdle is that the cells were produced by the Recombinant DNA technique, using retroviruses in plasmids.

The retroviruses are a class of viruses that actually insert themselves into the DNA strands of animal or plant cells to become a part of that cell’s DNA and are copied when the cell reproduces. They are manufactured in the lab in the form of plasmids in order to carry genes into the experimental cells.

Plasmids are little bits of DNA, a mini-virus in a circle. Think of a chain with pairs of magnets or interlocking puzzle pieces that connect the ends and make a loop. When open, the plasmid becomes a strand of DNA which has ends that are “sticky.” When placed in a culture with mouse or human cells, the plasmids infect the cells and then move into the nuclei of the cells. The retroviral DNA is inserted or inserts itself into the DNA of the host cell because the sticky ends of the plasmid strand match or mate to certain areas of the host DNA.

Plasmids can be manufactured to carry copies of genes that researchers want to insert into the DNA of experimental cells. The technique is common in commercial and experimental labs for at least the last 30 years. In fact, “Recombinant DNA” is used to induce strains of bacteria and yeast cells in cultures to manufacture vaccines like the flu and Hepatitis B vaccine and the insulin used by diabetics these days. The particular retroviruses used by Tamanaka are said to be “strongly silenced in humans.” In other words, they don’t normally get reproduced as viruses when the cell divides. Once they are taken up in the cell DNA, the viruses used in research don’t break out to become infectious viruses, again. However, some of them can induce the cells to form tumors or cancers if injected in an animal or human.

One of the possible problems that the article notes is that the new iPS cells each had several copies of the retrovirus included in their DNA. There is a concern that these bits may be responsible for the tumors that were seen in the mice used in the experiments. Before iPS can be used in humans, it will be necessary to learn to remove all the viral particles or to learn to make the cells without viruses that can cause tumors. Otherwise, there is a risk of causing cancer in patients.

The researchers note that another group of scientists have already reported that it is possible to insert one of the genes without using retroviruses and that the hope is to either find a way to insert the other three genes or to remove all traces of the virus.

There’s also a suggestion that what they are actually inducing to grow is a sub-set of fibroblasts with the tendency to become embryonic-like stem cells.

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Discussion

5 thoughts on “>Translation of Yamanaka, Yu "induced Pluripotent Stem Cells" (Revised)

  1. >I've been having a difficult time slogging through the science (my college biology class is 25 years in the past!) to understand the potential problems with the iPS cells. So thank you for this clear explanation.

    Posted by Lisa-Ann | November 30, 2007, 6:24 pm
  2. >Thank you! (It only took me a week and a half to get it clear enough in my mind to revise.)

    Posted by LifeEthics.org | November 30, 2007, 6:47 pm
  3. >"There's also a suggestion that what they are actually inducing to grow is a sub-set of fibroblasts with the tendency to become embryonic-like stem cells."I followed everything except this last sentence. What is "a sub-set of fibroblasts with the tendency to become embryonic-like stem cells"? Is the "they" here the same scientists you have been talking about throughout? In other words, is the suggestion that the iPS cells are really "fibroblasts with the tendency to become embryonic-like stem cells"? Would that be a problem?

    Posted by Lydia McGrew | December 1, 2007, 2:25 am
  4. >Whoops –the second reason:2. Lots of busy work to keep the Ph.D. candidates happy

    Posted by LifeEthics.org | December 2, 2007, 12:41 pm
  5. >Lydia, sorry I took so long to answer.The current thought is that not all fibroblasts are amenable to reprogramming. The researchers may be selecting – without intending to or knowing that they are – the group that is reprogrammed by the genes they're inserting.I think this may be good for two reasons: 1. If they find the exact cells that program, they can learn more about what they're doing – to be more efficient and to learn to use the technique in the body of sick patients instead of in the lab.

    Posted by LifeEthics.org | December 2, 2007, 12:41 pm

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