Abstract
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.
MeSH Terms
Animals
Bone Marrow Cells/cytology,immunology
Bone Marrow Transplantation/methods
Cell Lineage/immunology
Collagen/biosynthesis
Collagen Type I/biosynthesis
Collagen Type III/biosynthesis
Dermis/cytology,immunology
Disease Models, Animal
Endothelial Cells/cytology,immunology
Fibroblasts/cytology,immunology
Graft Survival/immunology
Green Fluorescent Proteins
Hematopoietic Stem Cells/cytology,immunology
Leukocyte Common Antigens/immunology
Mesenchymal Stem Cells/cytology,immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Skin/cytology,immunology,injuries
Transplantation Chimera
Wound Healing/genetics,immunology
Chemicals
Collagen Type I
Collagen Type III
Green Fluorescent Proteins
Collagen
Leukocyte Common Antigens
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Fathke Carrie
Department of Surgery, Box 356410, University of Washington Medical Center, 1959 NE Pacific Street, Seattle 98195, USA.
Wilson Lynne
Hutter Jonathan
Kapoor Vishal
Smith Andria
Hocking Anne
Isik Frank
References (20)
20 references, click to expand
-
Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow.
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3213-8
PMID: 10725391
-
Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice.
Surgery. 2000 Jun;127(6):696-704
PMID: 10840366
-
A role for hematopoietic stem cells in promoting angiogenesis.
Cell. 2000 Jul 21;102(2):199-209
PMID: 10943840
-
Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation.
Circ Res. 2000 Oct 27;87(9):728-30
PMID: 11055974
-
Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.
Nat Med. 2000 Nov;6(11):1229-34
PMID: 11062533
-
Bone marrow cells regenerate infarcted myocardium.
Nature. 2001 Apr 5;410(6829):701-5
PMID: 11287958
-
Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell.
Cell. 2001 May 4;105(3):369-77
PMID: 11348593
-
Peripheral blood fibrocytes: differentiation pathway and migration to wound sites.
J Immunol. 2001 Jun 15;166(12):7556-62
PMID: 11390511
-
Tissue dispersion and flow cytometry for the cellular analysis of wound healing.
Biotechniques. 2002 Mar;32(3):548-51
PMID: 11911658
-
Participation of bone marrow derived cells in cutaneous wound healing.
J Cell Physiol. 2003 Aug;196(2):245-50
PMID: 12811816
-
Fibroblast contraction of collagen lattices in vitro: inhibition by chronic inflammatory cell mediators.
J Cell Physiol. 1983 Sep;116(3):345-51
PMID: 6885932
-
Recipient preparation for bone marrow transplantation. I. Efficacy of total-body irradiation and busulfan.
Transplantation. 1988 Aug;46(2):205-10
PMID: 3043777
-
Immunolocalization of FXIIIa+ dendritic cells in human burn wounds.
J Surg Res. 1995 Sep;59(3):378-86
PMID: 7643597
-
Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair.
Mol Med. 1994 Nov;1(1):71-81
PMID: 8790603
-
Isolation of putative progenitor endothelial cells for angiogenesis.
Science. 1997 Feb 14;275(5302):964-7
PMID: 9020076
-
Role of alpha(v) integrins and angiogenesis during wound repair.
Wound Repair Regen. 1999 Sep-Oct;7(5):375-80
PMID: 10564566
-
Marrow stromal cells as stem cells for nonhematopoietic tissues.
Science. 1997 Apr 4;276(5309):71-4
PMID: 9082988
-
Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization.
Nat Med. 1999 Apr;5(4):434-8
PMID: 10202935
-
Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization.
Circ Res. 1999 Aug 6;85(3):221-8
PMID: 10436164
-
Cutaneous wound healing.
N Engl J Med. 1999 Sep 2;341(10):738-46
PMID: 10471461