Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo

Ekaterina Vorotnikova, Donna McIntosh, Abiche Dewilde, Jianping Zhang, Janet E. Reing, Li Zhang, Kevin Cordero, Khamilia Bedelbaeva, Dimitri Gourevitch, Ellen Heber-Katz, Stephen F. Badylak, Susan J. Braunhut*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

Most adult mammals heal without restorative replacement of lost tissue and instead form scar tissue at an injury site. One exception is the adult MRL/MpJ mouse that can regenerate ear and cardiac tissue after wounding with little evidence of scar tissue formation. Following production of a MRL mouse ear hole, 2. mm in diameter, a structure rapidly forms at the injury site that resembles the amphibian blastema at a limb amputation site during limb regeneration. We have isolated MRL blastemal cells (MRL-B) from this structure and adapted them to culture. We demonstrate by RT-PCR that even after continuous culturing of these cells they maintain expression of several progenitor cell markers, including DLK (Pref-1), and Msx-1. We have isolated the underlying extracellular matrix (ECM) produced by these MRL-B cells using a new non-proteolytic method and studied the biological activities of this cell-free ECM. Multiplex microELISA analysis of MRL-B cell-free ECM vs. cells revealed selective enrichment of growth factors such as bFGF, HGF and KGF in the matrix compartment. The cell-free ECM, degraded by mild enzyme treatment, was active in promoting migration and proliferation of progenitor cells in vitro and accelerating wound closure in a mouse full thickness cutaneous wound assay in vivo. In vivo, a single application of MRL-B cell matrix-derived products to full thickness cutaneous wounds in non-regenerative mice, B6, induced re-growth of pigmented hair, dermis and epidermis at the wound site whereas scar tissue replaced these tissues at wound sites in mice treated with vehicle alone. These studies suggest that matrix-derived products can stimulate regenerative healing and avert scar tissue formation in adult mammals.

Original languageEnglish
Pages (from-to)690-700
Number of pages11
JournalMatrix Biology
Volume29
Issue number8
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Blastema
  • Extracellular matrix
  • Tissue regeneration
  • Wound healing

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