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PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

  1. Yasufumi Kanedaa,1
  1. aDivision of Gene Therapy Science, and
  2. Departments of cDermatology,
  3. dNutrition and Physiological Chemistry, and
  4. eEnvironmental Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;
  5. bLaboratory of Biological Imaging, WPI-Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
  6. fSt. John's Institute of Dermatology, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom; and
  7. gDepartment of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA 19107

  1. Edited by Darwin J. Prockop, Texas A&M Health Science Center, Temple, TX, and approved March 18, 2011 (received for review November 10, 2010)

Abstract

The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 mo. The source of the epithelial progenitors was the nonhematopoietic, platelet-derived growth factor receptor α-positive (Lin−/PDGFRα+) bone marrow cell population. Skin grafts release high mobility group box 1 (HMGB1) in vitro and in vivo, which can mobilize the Lin−/PDGFRα+ cells from bone marrow to target the engrafted skin. These data provide unique insight into how skin grafts facilitate tissue repair and identify strategies germane to regenerative medicine for skin and, perhaps, other ectodermal defects or diseases.

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: tamai{at}gts.med.osaka-u.ac.jp or kaneday{at}gts.med.osaka-u.ac.jp.

  • Author contributions: K.T. designed research; K.T., T.Y., T.C., M.I., S.O., Y. Kikuchi, S.I., K.S., K.N., T.S., and N.U. performed research; J.-i.M. and J.T. contributed new reagents/analytic tools; K.T., I.K., and Y. Kaneda analyzed data; and K.T., J.A.M., J.U., and Y. Kaneda wrote the paper.

  • Conflict of interest statement: K.T., T.Y., and Y. Kaneda have filed patents relating to the use of HMGB1 for bone marrow cell mobilization and recruitment to damaged tissue. These individuals also hold stock in Genomix plc, a bio-tech company involved in HMGB1 translational research.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1016753108/-/DCSupplemental.

Freely available online through the PNAS open access option.

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