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Contribution of Bone Marrow–Derived Cells to Skin: Collagen Deposition and Wound Repair

Department of Surgery, University of Washington Medical Center, Seattle, Washington, USA

Key Words. Wound healing • Bone marrow • Stem cells • Mesenchymal stem cells • Hematopoietic stem cells • Collagen • Response to injury

Correspondence: Frank Isik, M.D., Department of Surgery, Box 356410, University of Washington Medical Center, 1959 N.E. Pacific Street, Seattle, Washington 98195, USA. Telephone: 206-543-5516; Fax: 206-543-8136; e-mail: isik{at}u.washington.edu

The bone marrow provides inflammatory cells and endothelial progenitor cells to healing cutaneous wounds. To further explore the bone marrow contribution to skin and healing wounds, we used a chimeric mouse model in which the bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice is transplanted into normal C57BL mice. We found that normal skin is a target organ for bone marrow–derived cells from both the hematopoietic and the mesenchymal stem cell pool. We present evidence that the bone marrow contribution to normal skin and the healing cutaneous wound is substantially greater than the previously recognized CD45⁺ subpopulation, where 15%–20% of the spindle-shaped dermal fibroblasts were bone marrow–derived (EGFP⁺). Furthermore, the bone marrow–derived cells were able to contract a collagen matrix and transcribe both collagen types I and III, whereas the skin-resident cells transcribed only collagen type I. Whereas endothelial progenitor cells were found early during the wound repair process, bone marrow–derived endothelial cells were not seen after epithelialization was complete. Our data show that wound healing involves local cutaneous cells for reconstituting the epidermis but distant bone marrow–derived cells and the adjacent uninjured dermal mesenchymal cells for reconstituting the dermal fibroblast population.

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