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Introduction to JID Symposium Proceedings 52nd Annual Montagna Symposium on the Biology of Skin “Stem Cells in Skin” Held at Snowmass, Colorado, USA, June 13–17, 2003

      The 52nd Annual Montagna Symposium on the Biology of Skin was held at Snowmass, Colorado, June 13–17, 2003. It followed in the tradition established in 1950 by Dr William Montagna, who established a forum where basic cutaneous biologists and clinically trained scientists met to discuss a single major topic in cutaneous biology. The topic for the 52nd Annual Montagna Symposium on the Biology of Skin was “Stem Cells in Skin.” As in the past symposia, the flow of presentations was designed to lead the discussion from the basic aspects of stem cell biology to potential clinical applications. Each presentation is presented in written form in the JID Montagna Symposium Supplement (September 2004).
      We began the symposium with a keynote presentation from Christopher Potten, who gave a superb overview of epithelial stem cell research for the last few decades. He highlighted both early and current ways of identifying stem cells through long-term retention of nuclear labels, which segued well into his current work demonstrating that small intestinal stem cells segregate their template and newly synthesized DNA. Over the next 3 d, we had five sessions of long talks with very lively discussion and one panel session on the potential for using stem cells in the clinic.

      Characterization and Location of Epithelial Stem Cells

      Using a whole mount labeling-retaining method, Kristin Braun identified clusters of stem cells in the hair follicles and interfollicular epidermis of mouse tails. She demonstrated that label-retaining cells (LRC) were not depleted during normal hair follicle cycles, but were depleted when TPA was added to the skin, and that these cells expressed expected stem cell markers. George Cotsarelis demonstrated that the stem cells clustered in the bulge of the hair follicle expressed keratin 15 and that many cancers derived from this area of the skin also were K15 positive, suggesting that the cancers were stem cell derived. Examining clusters of epithelial stem cells in the cornea, Robert Lavker discussed the identification and the current use of limbal stem cells for transplantation for various corneal disorders.

      Stem Cells in and from Tissues Other than the Skin

      William Harvey Fleming presented evidence for multilineage stem cells from the hematopoietic system that can produce both blood cells and endothelial cells, both of which can be found in various tissues after grafting. Ian Mackenzie demonstrated that the oral mucosa contains clonogenic cells that can produce several types of colonies, and that this may be a stem cell response to factors produced by the connective tissue. Robert Sackstein presented compelling data that cells in the bone marrow express a unique glycoform of CD44, which allows them to be induced to home to the skin. Thus the bone marrow and the skin may have several commonalities that have yet to be identified. Melissa Wong followed with her work demonstrating that the stem cell niche is highly regulated in the small intestine.

      Plasticity of Epithelial Stem Cells

      Examining the potential of adult epidermal stem cells, Jackie Bickenbach showed evidence that an epidermal stem cell placed in a developmental environment altered its cell fate no matter what its age. Pritinder Kaur demonstrated that both hair follicles and interfollicular epidermis had stem cells and that these stem cells contributed to various regions during wound healing.

      Regulatory Fate of Epithelial Stem Cells

      G. Paolo Dotto presented evidence that the size of the keratinocyte stem cell population can be regulated by interactions between the cell cycle pathway controlled by p21 and the signaling pathway controlled by notch 1. Examining several mouse strains and linkage analysis, Rebecca Morris showed that the proliferative capacity of stem cells and the sensitivity of skin to carcinogenesis may be linked through specific gene regulatory pathways. Dennis Roop followed with evidence that deregulation of the c-myc or p63 genes altered epidermal stem cell fates and could increase the potential of tumorogenesis and ectodermal dysplasia in the skin.

      Epidermal Stem Cells—Possible Therapeutic Uses

      Soosan Ghazizadeh demonstrated that epidermal keratinocytes could be transduced in vivo by a lentiviral vector carrying a reporter gene and that the stem cell progeny express this gene long term. Kyonggeun Yoon presented a non-viral gene targeting method that used a designed oligonucleotide to target a specific DNA sequence. Some of the cells showed long-term correction of the targeted gene. Both of these talks demonstrated a proof of principal that epidermal stem cells can be effectively targeted.

      Envisioning Adult Stem Cells in Clinical Practice

      The last session was a general discussion envisioning adult stem cells in clinical practice. The overall conclusion was that adult somatic stem cells could be used as a cell therapy in the future, and that any long-term gene therapy must target the stem cells, be expressed in the stem cell's progeny, and be able to be regulated appropriately.
      We ended with a banquet to honor David Norris for his dedication and leadership in maintaining the Montagna Symposium as William Montagna envisioned.
      This year the Eugene M. Farber Family generously provided support for outstanding young investigators to travel to the 52nd Montagna Symposium to present their research.

      The 2003 Eugene M. Farber Young Investigator Research Award Winners

      Dong Fang, Wistar Institute, Philadelphia, Pennsylvania.
      Derivation of melanocytes from human embryonic stem cells.
      Alessandra Marconi, Department of Dermatology, University of Modena, Modena, Italy. Keratinocyte stem cells are protected from anoikis via an integrin-signaling pathway: an insight into the molecular mechanisms.
      Simone Meindl, Department of Dermatology, University of Vienna, Vienna, Austria. The murine dermis harbors cells with in vitro hematopoietic clonogenic potential.
      Rick. P. Redvers, Peter MacCallum Cancer Center, Melbourne, Australia. Functional characteristics of the epidermal side-population: a candidate stem cell population.
      We greatly appreciate the 36 years of support of this conference by the National Institutes of Health and the current support by the National Institute of Arthritis, Musculoskeletal and Skin Diseases. We thank all who gave generously; the Symposium could not continue without the support of foundations, pharmaceutical companies, and the Eugene M. Farber Family. We also give a special thank you to Dr David Norris, whose leadership and dedication has kept this symposium going for the past 13 years.