International Society for Stem Cell Research 2011, ninth annual meeting in Toronto (June 15–June 18, 2011)

The International Society for Stem Cell Research ninth annual meeting in 2011 was held in Toronto, Canada. The meeting began within an earnest welcome by the president, Elaine Fuchs. The initial session was named “Past, Present, and Future” to showcase a historical perspective of stem cell research, and then presented information on how to implement stem cell based therapeutic strategies in humans. The marketing of stem cell therapies before their safety and efficacy have been demonstrated is an ongoing issue. Irving Weissman (Stanford University School of Medicine, USA) emphasized the importance of clear nomenclature in establishing the definition of any particular adult stem cell line. Single-cell clonality in conjunction with transplantation, as employed in the hematopoietic stem cell (HSC) field, he argued, is absolutely required for a rigorous definition of stem cells. He laid out a set of criteria that should be in place before marketing proceeds: (1) preclinical proof of principle; (2) verification of data in independent laboratories; (3) review by involvement of a medical ethics committee to protect the rights of human donors and their samples; and (4) approval by an official regulatory body such as the U.S. Food and Drug Administration (FDA). Ruth Lehman (New York University of School of Medicine, USA; Curr. Biol. 21, 1373-1379, 2011) discussed Piwi-interacting (pi) RNAs, which colocalize with H3K9me3 epigenetic marks at piRNA loci and showed how repression is conserved in the restriction of germ cell fate. Azim Surani (University of Cambridge, UK; Cell Stem Cell 4, 493-498, 2011) discussed a parallel model of reprogramming, namely reversion of epiblast stem cells to an embryonic stem cell (ESC)-like state. Two rounds of reprogramming occur in normal development: (1) just after fertilization; and (2) at embryonic Day 7.25 in mice. This seems to give a restriction rule for germline stem cells. An analogous reprogramming model was presented by Hans Schöler (Max Plank Institute for Molecular Biomedicine, Germany; Nat. Cell Biol. 13, 66-71, 2011). He discussed the reprogramming of postnatal somatic and germ cells, epiblast stem cells, and the utility of cell culture to ‘lock’ the epigenetic state of cells. He emphasized the critical role of endothelial cells in this area. Owen Tamplin (Zon Laboratory, Children's Hospital Boston, USA) presented the critical role of the sphingosine-1-phosphate receptor pathway in HSCs. This interferes with lipid signaling to determine the fate of HSCs in the vasculature before they migrate to the caudal hematopoietic tissues. Elaine Dzierzak (Erasmus Medical Center, The Netherlands; Blood, 117, 6132-6134, 2011; Blood, 117, 5088-5091, 2011) reviewed hematopoiesis, including the development of the first HSCs from the aorta-gonad-mesonephros (AGM) region. CD41 is present on both the AGM and yolk sac HSCs. Sean Morrison (University of Michigan, Ann Arbor, USA) reviewed the complexity of the HSC niche in adults, comprising a multicellular environment with potentially overlapping contributors from different cell types. HSCs residing in perivascular stromal cells secrete stem cell factor (SCF) for their own maintenance. This is the first genetic study of a key niche factor that promotes the maintenance of stem cells in the hematopoietic system. Margaret Goodells (Baylor College of Medicine, USA) reported that the loss of DNA methyltransferase in HSCs results in impairment of differentiation. Shosei Yoshida (National Institute for Basic Biology, Japan) described syncytial spermatogonia in mice and showed that spermatogonia are more dynamic and can revert or dedifferentiate to a stem cell state. Emi Nishimura (Tokyo Medical and Dental University, Japan; Cell Stem Cell 8, 177-187, 2011) presented the concept that tissue stem cells can themselves create the niche for other stem cell types, in which collagen XVII gene expression by hair follicle stem cells is required for the maintenance of adjacent melanocyte stem cells by providing TGFβ signaling. Scott Williams (Fuchs Laboratory, Rockefeller University, USA; Nature 470, 353-358, 2011) studied the regulation of switching between symmetric and asymmetric cell divisions during the construction of mammalian skin. Lentivirus shRNA, which is used to disrupt the gene that controls asymmetric cell division, caused functional defects in skin differentiation leading to hyperpermeability and skin thinning though aberrant loss of Notch signaling. Hans Clevers (Hubrecht Institute, The Netherlands; Cell 145, 851-862, 2011; Nature 476, 293-297, 2011) showed that adult stem cells are not all alike. He demonstrated that intestinal stem cells undergo symmetric divisions followed by the stochastic determination of daughter stem cells. Each crypt unit becomes monoclonal on a random basis, consistent with the model of neutral competition between stem cells. R-Spondin 1-mediated Wnt signaling is a critical downstream pathway for the differentiation of Lgr4/5-intestinal stem cells. Pier Paole di Fiore (Instituto FIRC di Oncologia, Molecolare, University of Genoa, Italy; Biochim. Biophys. Acta 1815, 26-43, 2011) discussed that the stem cell-like fraction of mammary tumors was shown to revert to a pattern of predominantly symmetric cell division. This was caused by the loss of p53 gene expression, as shown by partitioning of NUMB to both daughter cells using a vital staining. John Dick (University Health Network, Canada; Science 333, 218-221, 2011; Nature 469, 362-367, 2011) reported two important findings. First, the identification and profiling of single-cell clones of functionally pure human HSCs and second, how to model the clonal diversity of cancer stem cells in leukemia. CD49f is expressed in human HSCs and the authors achieved long-term multilineage engraftment of single human cells in immunocompetent mice, using Thy1+ Rodamine 123lo CD49f+ cells. Loss of CDKN2A/B was associated with increased aggressiveness and competitiveness of leukemia-initiating cells. Alysson Muotri (University of California, San Diego, USA; Cell 143, 527-539, 2010) found on de novo L1 retrotransposon insertions in induced pluripotent stem cells (iPSCs)-derived neurons from patients with Rett syndrome and autism spectrum disorders. The study of somatic mosaicism is highly relevant to the future of iPSC-based therapy. Athurva Gore (University of California, San Diego, USA) and Uri Ben-David (The Hebrew University, Israel; Cell Stem Cell 7, 521-531, 2010) described studies on the genetic variation and karyotype abnormalities that arise as a consensus of selection and cloning of primary cells in culture and also on the generation of iPSCs. Irina Conboy (University of California, Berkeley, USA; Aging 3, 556-563, 2011) hypothesized that muscle stem cells remain young while the surrounding niche ages. Amy Wagners (Harvard University, USA) also described cultured satellite muscle cells as potential tools for discovery of new bioactive molecules for treating muscle diseases. Michael Rudnicki (Ottawa Hospital Research Institute, Canada) discussed the biochemical modulation of transcription factors in muscle satellite cell differentiation. Takayuki Tanaka (Kyoto University, Japan) found that a substantial fraction of cases of chronic infantile neurological cutaneous and articular syndrome are caused by somatic mosaic NLRP3 mutations, leading to both cell-autonomous and non-cell autonomous macrophage-dependent effects in a dominant manner. Shinya Yamanaka (Kyoto University, Japan; Nature 474, 225-229, 2011) presented the efficient application of nuclear reprogramming technology in embryos for avoiding mutation. He has discovered that Glis1 compensates very effectively for the use of c-Myc to generate iPSCs without causing oncogenic side effects. He also demonstrated that the inconsistent data of iPSCs with ESC reported by other researchers are associated with the higher ‘stemness’ quality and pluripotency of iPSCs. Some of the most exciting progress continued to be in the development of new therapies for those suffering from disease- or injury-related blindness. Michele De Luca (University of Milan, Italy; N. Engl. J. Med. 363, 147-153, 2010) described progress in delivering autologous limbal cells implanted surgically implanted back into the patient's damaged eye. In more than 75% of cases, corneal regeneration was restored and was stable for long as 10 years, attributed to p63+ holoclones observed in the limbal outgrowths. A promising application of human ESCs is in the treatment of macular degeneration. Peter Coffey (University College London, UK) reported the progress of a therapy for macular degeneration by transplanting human ESC-derived pigmented retinal epithelial cells. Peter Zandstra (University of Toronto, Canada) described the large-scale culture of pluripotent stem cells in suspension: differentiating as ‘in-line’ for ready use. Christopher Breuer (Yale University School of Medicine, USA) described early clinical trials of a tissue-engineered vascular graft for the treatment of congenital heart defects. He identified macrophages as both the culprit in stenosis, a complication seen in a number of patients, and as the driver of neovessel formation. This result suggests the possibility of therapeutic approach using a cell-free biomimetic scaffold to enhance innate regenerative mechanisms while minimizing the risk of occlusion. Richard Young (Massachusetts Institute of Technology, USA; Cell 144, 940-954, 2011) and Stuart Orkin (Children's Hospital Boston, USA; Cell 145, 835-850, 2011) presented the identification of mechanisms that regulate the switch for self-renewal and differentiation in pluripotent stem cells. Judy Lieberman (Harvard Medical School, USA) conveyed the results of a recent genome-wide siRNA screening and identified the inhibitors of breast-cancer-tumor-initiating cells, in breast cancers. The 2011 Outstanding Young Investigator award was presented to Robert Blelloch (University of California, San Francisco, USA; Nature 463, 621-626, 2010), who screened the microRNAs (miRNAs) that influence self-renewal and factors for the formation of mouse ESCs. He also reported that the opposing miRNA families (ESCs and let-7 miRNAs) caused reprogramming in human iPSCs by influencing pathways related to the mesenchymal-to-epithelial cell transition (MET). The McEwen Centre Award for innovation was given to Takahasi and Yamanaka. The Anne McLaren Memorial Lecture was given by Nicole Le Douarin (Académie Des Sciences, Paris, France), who studied neural crest function using quail/chicken chimeras. This meeting in 2011 gave the impression that the field of stem cell research is maturing rapidly and is increasing the rate of development of clinical applications for novel stem cell treatments. We are sure to hear more about how stem cell research is changing the face of science, increasing our understanding of disease, and prompting the development of new therapies.

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