Distant mesenchymal progenitors contribute to skin wound healing and produce collagen: evidence from a murine fetal microchimerism model

PLoS One. 2013 May 1;8(5):e62662. doi: 10.1371/journal.pone.0062662. Print 2013.

Abstract

The contribution of distant and/or bone marrow-derived endogenous mesenchymal stem cells (MSC) to skin wounds is controversial. Bone marrow transplantation experiments employed to address this have been largely confounded by radiation-resistant host-derived MSC populations. Gestationally-acquired fetal MSC are known to engraft in maternal bone marrow in all pregnancies and persist for decades. These fetal cells home to damaged maternal tissues, mirroring endogenous stem cell behavior. We used fetal microchimerism as a tool to investigate the natural homing and engraftment of distant MSC to skin wounds. Post-partum wild-type mothers that had delivered transgenic pups expressing luciferase under the collagen type I-promoter were wounded. In vivo bioluminescence imaging (BLI) was then used to track recruitment of fetal cells expressing this mesenchymal marker over 14 days of healing. Fetal cells were detected in 9/43 animals using BLI (Fisher exact p = 0.01 versus 1/43 controls). These collagen type I-expressing fetal cells were specifically recruited to maternal wounds in the initial phases of healing, peaking on day 1 (n = 43, p<0.01). This was confirmed by detection of Y-chromosome+ve fetal cells that displayed fibroblast-like morphology. Histological analyses of day 7 wounds revealed vimentin-expressing fetal cells in dermal tissue. Our results demonstrate the participation of distant mesenchymal cells in skin wounds. These data imply that endogenous MSC populations are likely recruited from bone marrow to wounds to participate in healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Tracking
  • Chimerism
  • Collagen
  • Collagen Type I / genetics
  • Collagen Type I / metabolism*
  • Female
  • Fetus / cytology*
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pregnancy
  • Skin / cytology*
  • Skin / metabolism
  • Wound Healing*

Substances

  • Collagen Type I
  • Collagen

Grants and funding

This work was funded by the National Health and Medical Research Council in Australia, project grant #569822. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.