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Strategies to enhance epithelial–mesenchymal interactions for human hair follicle bioengineering

      Abstract

      Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Accordingly, the enhancement of this crosstalk represents a promising approach to achieve successful bioengineering of human hair follicles. The present article summarizes the techniques, both currently available and potentially feasible, to promote epithelial–mesenchymal interactions (EMIs) necessary for human hair follicle regeneration. The strategies include the preparation of epithelial components with high receptivity to trichogenic dermal signals and/or mesenchymal cell populations with potent hair inductive capacity. In this regard, bulge epithelial stem cells, keratinocytes predisposed to hair follicle fate or keratinocyte precursor cells with plasticity may provide favorable epithelial cell populations. Dermal papilla cells sustaining intrinsic hair inductive capacity, putative dermal papilla precursor cells in the dermal sheath/neonatal dermis or trichogenic dermal cells derived from undifferentiated stem/progenitor cells are promising candidates as hair inductive dermal cells. The most established protocol for in vivo hair follicle reconstitution is co-grafting of epithelial and mesenchymal components into immunodeficient mice. In theory, combination of individually optimized cellular components of respective lineages should elicit most intensive EMIs to form hair follicles. Still, EMIs can be further ameliorated by the modulation of non-cell autonomous conditions, including cell compartmentalization to replicate the positional relationship in vivo and humanization of host environment by preparing human stromal bed. These approaches may not always synergistically intensify EMIs, however, step-by-step investigation probing optimal combinations should maximally enhance EMIs to achieve successful human hair follicle bioengineering.

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      Biography

      Manabu Ohyama received his MD and PhD degrees from Keio University Tokyo, Japan, in 1993 and 2002 respectively. During 2002–2005, he was a visiting fellow of Dr. Jonathan C. Vogel's laboratory at the Dermatology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. He is currently a Senior Assistant Professor at the Department of Dermatology, Keio University School of Medicine and in charge of the hair disease clinic at Keio University Hospital. His current interests are in the pathophysiology of hair disorders, hair follicle stem cell biology and regenerative medicine of the skin. He has been a Deputy Secretary General and a board member of Japanese Society for Investigative Dermatology (JSID) from 2010 and 2006 respectively. He received the William J. Cunliffe Scientific Award at the 15th annual meeting of European Academy of Dermatology and Venereology and JSID's fellowship Shiseido Award in 2008.

      Biography

      Ophelia Veraitch received her MB BS BSc (Hons.) degrees from Imperial College London in 2006. During 2006–2010 she completed her Core Medical Training in the Chelsea and Westminster, Charing Cross, St. Mary's and the Hammersmith Hospitals, London and obtained her MRCP (UK). She is currently enrolled in the PhD program at the Department of Dermatology, Keio University School of Medicine.