Embryonic Stem Cell Derived NK cells
Dan S. Kaufman 2009. Toward clinical therapies utilizing hematopoietic cells derived from human pluripotent stem cells. Blood. Prepublished online August 4, 2009.
George Q. Daley and David T. Scadden. 2008. Prospects for Stem Cell-Based Therapy. Cell 132. P544-548.
Xinghui Tian and Dan S. Kaufman, 2008. Differentiation of embryonic stem cells towards hematopoietic cells: progress and pitfalls. Current Opinion in Hematology 2008, 15:312–318.
Woll PS, Grzywacz B, Tian X, Marcus RK, Knorr DA, Verneris MR, Kaufman DS. 2009. Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity. Blood. 113(24):6094-101.
Please tell us a bit about yourself and your research and how you got started in the field of stem cells.
Can you briefly describe the “two-step” method you used to derive NK cells from ESC? In your description can you please address what the significance of observing embryoid body formation in Serum-free systems is? And why serum-free conditions are necessary for this?
Yvanka De Soysa
Your paper relies heavily on defining a mature natural killer cell based on a series of different markers. Can you summarize the classes of these markers for us and what significance they actually have to NK structure and function?
These hESC-NK cells are extremely effective and are very close to typical endogenous NK cells when phenotyped for the cell markers, however, the hESC-NK cells do not express CD161 while the UCB-NK do. Can you explain why it does not express this cytotoxic receptor and do you think there is a significant functional difference to this?
If a more reliable protocol for differentiating NK cells from umbilical cord blood (UCB) existed at the moment, do you believe that treatments with hESC-derived NK cells would be equivalent to treatments with UCB-derived NK cells?
You have mentioned that hESCs and UCB progenitors develop into NK cells along different paths, and that hESCs may differentiate in a faster developmental pathway. This seems contradictory in the sense that UCB progenitors are already in theory closer to the final cell fate of NK cells then an ESC. So why do you think this is the case?
Why did your lab group choose to work with the H9 line? Do you have any doubts that hESC-NK cells derived from a different line would not work as effectively as those derived from the H9 line? How many more experiments, say with different ESC lines, are necessary before we can start human clinical trials with this SC cancer therapy and ultimately prescribe this therapy to cancer patients?
Do ESC verse adult stem cells like HSCs behave differently when transplanted into or homed to a particular tissue for repair? Do they eventually die out or are they present for a very long time? Are there any potential side effects these cells may possess, such as tumorogenesis? How do scientists like yourself attempt to combat these types of potential side effects of stem cell therapies?
In one of the papers, it talked about the potential of using one adult somatic cell and reprogramming it into another in a way that completely skips the process of reverting to the pluripotent state. Could you elaborate on how this might be possible and how you would use it in your research?
Can you please compare the potential of iPSC and hESC to create viable long-term, multi-lineage cells for transplantation or other treatment in humans? Based on your opinions on this topic, how do you think IPS cell research will help to overcome some of the challenges you’ve faced, particularly allogeneic immune responses? Do you think IPS cell therapies will realistically overcome the challenges that the concept of a “stem cell bank” propose?
Currently in your opinion what are the most pressing questions in the field of Embryonic Stem Cell Research and their use in human disease therapy, and what steps is your lab taking to address those questions?