View from the floor: ISSCR day 2

By Ben Paylor

Although elsewhere in Canada there are some very troubling consequences arising from a group not living up to their potential (I refer to the rioting hooligans and not the Canucks), the realization of potential happening here at the ISSCR couldn’t be more different. There is a great sense of excitement and buzz surrounding the wide variety of presentations, which cover the entire breadth of stem cell research being conducted worldwide, With over 4,000 members in attendance, the ISSCR is the largest stem cell conference in the world and we are lucky to have it here this year. A quick glance at the 1,400 poster abstracts and one finds 270 categorized as embryonic stem cells, 180 on mesenchymal stem cells (a term Irv Weissman yesterday suggested should be used with more scrutiny), 200 on inducible pluripotent stem cells and reprogramming, 150 on stem cell technology and tissue engineering, and nearly 350 on a menagerie of tissue-specific stem cells. The sheer quantity of talks and posters can be a little bit daunting, but the opportunity for learning, networking, and collaboration makes the stakes too high for one to be overwhelmed.

Hans Clevers, the director of the Hubrecht Institute in Utrecht, closed the morning plenary session, “Tissue Stem Cell Origins”. His talk on a population of stem cells labeled by LRG5 was excellent, aided by numerous colorful and understandable CGI animations of the data they were generating. Following the observation that LRG5 labels a specific progenitor cell population in the intestinal crypts, his group employed a number of lineage tracing strategies to elegantly show how a single group of stem cells can continually divide and differentiate in order to repopulate this organ which continually regenerates through mammalian life. The use of the Rainbow reporter strain to this effect produced some very revealing (and colorful) data demonstrating how this repopulation occurred. The ability of a single LRG5+ cell from the crypt to generate clonal structures he termed as “miniguts” was remarkable, with this effect being improved if the cells were isolated as doublets with their paracrine partners, paneth cells. By combining CGI animation with elegant data, his talk provided a very clear and comprehensive overview of some of the work being done at the Hubrecht Institute.

In the afternoon, the main auditorium was stirred up somewhat by Thea Tlsty’s presentation describing the isolation and characterization of pluripotent stem cells from adult mammary tissue. The time available for questions was very limited, and a number of members of the audience, myself included, wish there had been a little more time to discuss the results and their significance. Later in the afternoon, the inaugural Ernest McCulloch Memorial Lecture was given by John Dick on the genetic diversity of leukemia initiating cells. It was a captivating and detailed presentation outlining the need for standardization of experimental design in the field of cancer stem cells, as well as a comprehensive update on characterization of HSC developmental hierarchy. Controversy surrounding the concept of cancer stem cells is well known in the field, and Dr. Dick argued that perhaps competing theories need not be considered to be mutually exclusive. He conceptually outlined how clonal evolution and cancer stem cell hypothesis are perhaps more complementary than some might think, and presented some data from an acute lymphoblastoma leukemia model which supports this theory. It was an excellent end to day 2 of the conference.

Photo: LRG5 labelled cells in intestinal crypts, Hans Clevers lab

Comments

[Ben Paylor]

Hey Alexey!
You are correct about Dr. Dick's thoughts on targeting leukemic stem cells, he feels it will be more difficult than some might think. He discussed data from his group on genetic diversity within leukemia inducing cells, but I don't recall too much mention of genetic plasticity. He certainly feels that there will be difficulty for therapies aimed at patient specific targeting of all leukemic stem cells as there is such diversity in rare subclones within each cancer.

As for Irv's comments on cultured bone marrow stromal cells is that it is difficult to ascertain if they are stem cells, that is "self renewing single cells which give rise to clonal progeny of a number of mature cell types". He added, "Accurate language with names based on evidence would help: most are mesenchymal stromal cells, not mesenchymal stem cells. Other functions in transplantation may be valuable when determined and reported"

Hope that helps!

[Alexey Bersenev]

Thanks for the coverage guys!
Can you give more details on Irv Weissman's opinion about MSC? Why he said so and what did he mean?

Did Dr. Dick said something about leukemic stem cell genetic plasticity? Mean switching genotype back and forth. Which could be different from diversity. How he proposed to target leukemic stem cells then? According him, targeting of leukemic stem cells is elusive. Is that correct?