title: Wound repair by bone marrow stromal cells through growth factor production.
abstract: We have previously shown that treatment with bone marrow stromal cells (BMSCs) augments the healing of fascial wounds in the rat. However, the biochemical mechanism by which BMSCs improve wound healing was not investigated. Growth factors have been shown to play a key role in repairing damaged tissue. In this study, we investigated whether BMSCs are capable of producing growth factors that play a critical role in healing of the damaged tissue. Growth factor expression in BMSCs stimulated with pro-inflammatory cytokines or wound superfusate was measured by RT-PCR and growth factor-specific quantitative sandwich enzyme-linked immunosorbent assay (ELISA). RT-PCR analysis demonstrated that BMSCs are capable of expressing transforming growth factor beta-1 (TGF-beta1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) platelet-derived growth factor (PDGF), keratinocyte growth factor (KGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF) constitutively or upon stimulation with LPS, IL-1alpha, or TNF-alpha. Quantitative analysis of growth factor production by ELISA showed that BMSCs do not secrete TGF-beta1, EGF or VEGF in response to uninjured fascia tissue superfusate; however, production of these growth factors is significantly increased when cells were stimulated with wound tissue superfusate. The ability of wound to stimulate growth factor production in BMSCs could be detected as early as day 1 and lasted through day 7 after wounding. Thus, growth factor production by BMSCs in response to wound microenvionment suggests that BMSCs might augment wound healing through the responsive secretion of growth factors that enhance angiogenesis and promote wound repair.
authors.affiliation: Department of Surgery, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Dulchavsky
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gao
authors.forename: David
authors.initials: D
authors.lastname: Kwon
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Scott
authors.initials: S
authors.lastname: Dulchavsky
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Gautam
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D005205:Fascia / Q000166:cytology / Q000502:physiology*; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000637:transplantation*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D051523:Fibroblast Growth Factor 7; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor