title: Bone marrow cell mobilization by the systemic use of granulocyte colony-stimulating factor (GCSF) improves wound bed preparation.
abstract: Innovative approaches are needed to accelerate the healing of human chronic wounds not responding to conventional therapies. An evolving and promising treatment is the use of stem cells. Our group has previously described the use of expanded (in vitro) autologous stem cells aspirated from human bone marrow and applied topically in a fibrin spray to human acute and chronic wounds. More recently, we have sought ways to mobilize stem cells directly from the bone marrow, without in vitro expansion. In this report, we show that systemic injections of granulocyte colony-stimulating factor (GCSF) can mobilize stem cells from bone marrow into the peripheral blood and then to the wound site. Our objectives were to optimize parameters for this method by using mouse models and proof of principle in a human chronic wound situation. Mice were injected for 5 days with 2 different formulations of GCSF and compared to control saline. To monitor stem cell mobilization, flow cytometric measurements of Sca-1 and c-Kit and colony-forming cell assays were performed. Full-thickness tail wounds in mice were created and monitored for healing, and polyvinyl alcohol sponges were implanted dorsally to assess collagen accumulation. To determine bone marrow stem cell homing to the wound site, chimeric mice transplanted with Green Fluorescent Protein bone marrow cells were scanned by live imaging. Additionally, as proof of principle, we tested the systemic GCSF approach in a patient with a nonhealing venous ulcer. Our findings lay the ground work and indicate that the systemic administration of GCSF is effective in mobilizing bone marrow stem cells into the peripheral blood and to the wound site. These findings are associated with an increased accumulation of collagen and promising results in terms of wound bed preparation and healing.
authors.affiliation: 1Boston University School of Medicine, Boston, MA, USA.
authors.forename: Satori
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lin
authors.forename: Ron
authors.initials: R
authors.lastname: Ramirez
authors.forename: Polly
authors.initials: P
authors.lastname: Carson
authors.forename: David
authors.initials: D
authors.lastname: Fiore
authors.forename: Jane
authors.initials: J
authors.lastname: Goodrich
authors.forename: Tatyana
authors.initials: T
authors.lastname: Yufit
authors.forename: Vincent
authors.initials: V
authors.lastname: Falanga
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D017719:Diabetic Foot / Q000188:drug therapy*; D004195:Disease Models, Animal; D016903:Drug Monitoring; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008875:Middle Aged; D016896:Treatment Outcome; D014647:Varicose Ulcer / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: chronic wounds; granulocyte colony-stimulating factor (GCSF); leg ulcers; stem cells; wound bed preparation; wound healing