Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay

B. A. Bromberek, P. A.J. Enever, D. I. Shreiber, M. D. Caldwell, R. T. Tranquillo

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Rat dermal fibroblasts were dispersed initially in the outer shell of a fibrin gel sphere, while the inner core either was devoid of cells or contained peritoneal exudate cells (primarily macrophages), thereby mimicking the inflammatory phase of wound healing. The fibroblasts compacted floating fibrin microspheres over time. In the absence of macrophages, the initial distribution of fibroblasts (only in the shell) induced circumferential alignment of fibrin fibrils via compaction of the shell relative to the core. The aligned fibrils created a contact guidance field, which was manifested by strong circumferential alignment of the fibroblasts. However, in the presence of macrophages, the fibroblasts exhibited more radial alignment despite the simultaneous contact guidance field in the circumferential direction associated with compaction. This was attributed to a chemotactic gradient emanating from the core due to a putative factor(s) released by the macrophages. The presence of a radial chemotactic stimulus was supported by the finding of even greater radial alignment when fibrin microspheres were embedded in an agarose-fibrin gel that abolished compaction and consequently the contact guidance field. Our assay permits the simulation of tissue morphogenetic processes that involve cell guidance phenomena and tractional restructuring of the extracellular matrix.

Original languageEnglish (US)
Pages (from-to)230-242
Number of pages13
JournalExperimental Cell Research
Volume275
Issue number2
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
This work has been supported by NIH P01-GM50150-03S1 (R.T.T.). Drs. Terrence Ryan, George Cherry, and David Knighton are gratefully acknowledged for the use of laboratory facilities as are Vance Fiegel, Amy Tranquillo, Matt McCoy, Jim Pray, Tim Johnson, and Cheryl Wotus for technical advice and assistance during the early phases of this project. The technical advice and assistance of Jeff Shearer, Ray Sicard, and Cindy Coulter are also gratefully acknowledged as is the assistance Allison Bain with statistical testing.

Keywords

  • Chemotaxis
  • Coculture assay
  • Contact guidance
  • Fibrin gel
  • Fibroblasts
  • Macrophages
  • Wound healing

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