title: Conversion from human haematopoietic stem cells to keratinocytes requires keratinocyte secretory factors.
abstract: BACKGROUND
  Recent studies have reported that bone-marrow-derived stem cells (BMSCs), including haematopoietic stem cells (HSCs) and mesenchymal stromal cells, differentiate in order to regenerate various cellular lineages. Based on these findings, it is known that BMSCs can be used clinically to treat various disorders, such as myocardial infarction and neurotraumatic injuries. However, the mechanism of HSC conversion into organ cells is incompletely understood. The mechanism is suspected to involve direct cell-cell interaction between BMSCs, damaged organ cells, and paracrine-regulated soluble factors from the organ, but to date, there have been no investigations into which of these are essential for keratinocyte differentiation from HSCs.
  
  
  OBJECTIVE
  To elucidate the mechanism and necessary conditions for HSC differentiation into keratinocytes in vitro.
  
  
  METHODS
  We cultured human (h)HSCs under various conditions to try to elucidate the mechanism and necessary conditions for hHSCs to differentiate into keratinocytes.
  
  
  RESULTS
  hHSCs cocultured with mouse keratinocytes induced expression of human keratin 14 and transglutaminase I. Only 0.1% of the differentiated keratinocytes possessed multiple nuclei indicating cell fusion. Coculture of hHSCs with fixed murine keratinocytes (predicted to stabilize cellular components) failed to induce conversion into keratinocytes. Conversely, keratinocyte-conditioned medium from both human and mouse keratinocytes was found to mediate hHSC conversion into keratinocytes.
  
  
  CONCLUSIONS
  Human HSCs are capable of differentiation into keratinocytes, and cell fusion is extremely rare. This differentiating is mediated by the plasma environment rather than by direct cell-cell interactions.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. yfujita@med.hokudai.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: D
authors.initials: D
authors.lastname: Inokuma
authors.forename: R
authors.initials: R
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002459:Cell Fusion; D002478:Cells, Cultured; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053547:Keratin-14; D011503:Transglutaminases; C105804:transglutaminase 1