Everything you always wanted to know about stem cells, but were afraid to ask!

A year ago, I offered to answer readers questions about stem cells. Any questions. I’m making that offer again…ask away in the comments sections or send me an email knoepfler AT ucdavis DOT edu.

 

I’ll do my best to answer and if I don’t know the answer, I’ll look into it. Don’t be shy.

 

8 Comments


  1. Thanks for the offer…and I hope asking two questions is OK. The first is how great the risk is of teratoma formation from using cells differentiated from hESC. Can researchers use cell sorting and other techniques to get pure enough samples of differentiated cells so that the risk of teratoma formation is very low? Geron claims to have seen zero teratoma in it pre clinical work on it’s OPC1 cells in rats, presumably due to it’s ability to generate relatively pure batches of differentiated cell. What are your thoughts on this?

    The second question is on the degree to which differentiated cells derived from hESC are immune privileged. Any recent developments on this from? (this question has particular relevance in the wake of last week’s news regarding iPS cells.)


  2. Hi Dr. Paul,
    Also a thank you for your time, and info. My question has to do with Parthenogenic Cells.

    I understand they have only half of the DNA variations, and they produce fewer immune reactions, yet I never read about them as a viable cell type. What do you know about them?

    Thanks,
    Matt


  3. @Mike
    Hi Mike,
    Regarding your first question, the unfortunate answer is that we just do not know the risk of teratoma formation in humans. However, everything I’ve heard is that the preclinical studies were indeed very encouraging. The whole point of the Phase I and Phase I/II trials of Geron and ACT is to address safety. So we shall see. We do cell sorting all the time. It is a very powerful technique but not perfect. An expert on sorting once told me there is no such thing as a pure population of cells. The good news is that not all ES cells can form teratoma and in fact most people think it takes thousands, maybe tens of thousands of ES cells in order to generate a teratoma. As a result, sorting does not have to be perfect. The bottom line is while the jury is still out on safety of hESC-based therapies, it is reasonable to hope that they will prove safe. As I have posted in the past, if you do enough of these therapies (say treat thousands of patients in the future), someone will eventually get a teratoma, but even something as seemingly benign as aspirin kills people if enough people take it. It all boils down to benefit vs. risk.
    Regarding your second question, I am conflicted on that issue. As a scientist, I have a tough time imagining how differentiated cells derived from ES cells could possibly be immune privileged when used as an allotransplant. Maybe ES cells themselves might have some degree of immune privilege, but why would differentiated cells? On the other hand, there are numerous reports which seem to indicate there is indeed at least some level of immune privilege. Reportedly Geron is only using transient immunosuppression in their trial. I guess this remains a fairly controversial area.
    Paul


  4. @Matt
    Hey Matt,
    Great question. I wish there were great answers. Parthenogenetic cells are produced from eggs that undergo induced or (in non-mammals) spontaneous parthenogenesis. There have been a lot of conflicting results on human parthenogenesis and even some scandals.
    Parthenogenic stem cells such as embryonic stem cells would be XX and hence female, but all the DNA would only come from a female. In theory this might make it less immunogenic. A lot of the time parthenogenesis might lead to failed development or abnormalities. I’m not an expert in this area, but I’m skeptical about it.


  5. Hi Dr. Paul.
    This is not a question, but rather a suggestion for someone wishing to follow a path that no one else has followed. Your comments would be appreciated.
    This suggestion may possibly explain why 99.9% of seed cells do not turn into iPS cells and why probably nearly all iPS cells have small genetic differences to human ES cells. Has anyone explained these two points yet?
    The main thrust of my proposal is that monocytes have the capability of differentiating into any somatic cell in the body. This uses the normal cellular regeneration process. If so, the monocyte; with the correct signalling; has the same power as an iPS cell, with the extra benefit that it can be reproduced in an autologous way. If I am correct, the iPS cells that are presently being produced, come from the bovine (or any other type of animal) serum that is added to the original medium. I am suggesting that the current process is not converting skin or olfactory cells to iPS cells, instead the monocytes in the “bovine” serum are being converted to “iPS” cells. This would be a much shorter and easier process than reprogramming a fully differentiated skin cell to a pluripotent stem cell. This would require the reversal of many more pathway steps.
    If the “bovine” monocyte is not 100% the same as the human monocyte, there is the potential of tissue rejection if used in humans. If using mice, any serum used should come from healthy genetically identical mice, this should stop tissue rejection in other mice when using differentiated cells. If iPS cells really come from “skin” cells you should expect most of the skin cells to be reprogrammed into iPS cells. If iPS cells come from monocytes, you would only expect say 0.1% or less of the total cells to be reprogrammed.
    If researchers tried to produce their results without monocytes in their serum it would prove whether they, or I am correct. Another way of proving who is correct is to grow a purified strain of monocytes and use this on their medium to see if the production of iPS cells increase significantly. This should really be worth trialling.

    Because of a supply problem in using human serum in research, I would expect the existing technology to be used in mice research (using mice serum); and human serum, or purified human monocytes, to be used when preparing to conduct human trials. If my suggestion is proven, it will lead to a proposed new alternative to embryonic and iPS stem cells which has the potential to eliminate most known problems in existing stem cell research.


  6. @D. Hicks
    iPS cells likely have genetic differences because the reprogramming process is very harsh.
    I don’t believe that monocytes explain iPS cells. First, monocytes are not pluripotent like iPS cells. Also, for human iPS cells, bovine serum is not used at all. Even if bovine serum is used for say a mouse iPS cell production experiment, bovine serum is repeatedly filtered through 0.2 micron filters and monocytes are several microns in diameter. I have been using bovine serum for 20 years and have never seen any cells of any kind in it, monocytes or otherwise.


  7. Hi Paul,

    I have a question that came to mind.

    Are there any hESC lines available that are blood type O negative? From my readings it seems like there either aren’t any, or it not publically disclosed.

    Obviously this would be very useful for anyone that wanted to develop hESC derived universal blood. ACT has been working on deriving red blood cells and platelets, but it seems they are not type O negative.

    The blood market is absolutely massive, so I have always been curious why this has not been discussed more in the outlets I follow.


  8. Thanks Paul for your quick answer,
    I have no knowledge of what makes up the total medium. Is it possible then that the medium and not the serum contains a very small percentage of monocytes?
    I am not proposing that monocytes may be pluripotent, only that they have the capability to produce the recipe to regenerate any somatic cell in the body and initiate a feed back loop to the bone marrow. They would normally do this by providing the required signalling, (with the help of autophagy and T cells). This is an alternative proposal to existing stem cell research.

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