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Transplantation of mesenchymal stem cells and fibroblasts in a bio‐compatible matrix corrects defective dermal remodeling
Author(s) -
Yates-Binder Cecelia C,
Rodrigues Melanie,
Whaley Diana,
Wells Alan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.399.3
Subject(s) - mesenchymal stem cell , wound healing , scars , transplantation , regeneration (biology) , paracrine signalling , extracellular matrix , microbiology and biotechnology , fibroblast , fibrosis , matrix (chemical analysis) , medicine , stem cell , cancer research , pathology , immunology , chemistry , biology , surgery , in vitro , receptor , biochemistry , chromatography
Curative molecular therapies are needed to correct matrix dysfunctions that results in scar formation upon healing. Mesenchymal stem cell transplantation has been reported to enhance healing however the mechanism for this response is unknown. The possibilities include the restorative paracrine effects of MSC synthesized soluble factors on dermal cells and matrix expression. This study examines the influence MSC's have on matrix remodeling in vivo. We recently developed a chronic wound scar model based on the absence of wound resolution through CXCR3 signaling axis; these mice develop sterile chronic inflammation and hypertrophic scars. Using fibroblasts encapsulated with MSC's in a biocompatible matrix, we determined that fibroblasts could overcome endogenous deficiencies and generate a more physiological dermal tissue. Xenotransplantation of CXCR3−/− mouse fibroblast and hMSC's into wounds of CXCR3−/− mouse scarring model revealed an increase in survival and reduced apoptosis, enhanced healing response, correction of matrix regeneration, and reduced inflammation during the first 30 days. Changes in matrix and soluble signals were also examined. These data suggest in situ matrix composition and mature matrix generation regulates scarring. This study provides insight into conceptual therapies of cell transplantation, by altering soluble factors, as viable for antifibrotic treatment.