title: Mesenchymal stem cells facilitate fracture repair in an alcohol-induced impaired healing model.
abstract: OBJECTIVE
  Clinical studies have shown alcohol to be a risk factor for traumatic orthopaedic injuries and for nonunion. Data from animal studies suggest that alcohol exposure inhibits fracture healing. This report presents a novel rodent model of impaired fracture healing caused by repeated alcohol exposure. Using this model, we examined the regenerative effects of an intravenously administered population of isolated and expanded mesenchymal stem cells (MSCs) on fracture healing.
  
  
  METHODS
  Bone marrow-derived MSC were isolated from transgenic green fluorescent protein C57BL/6 mice, and culture expanded using a lineage depletion protocol. Adult wild-type C57BL/6 mice were subjected to a 2-week binge alcohol exposure paradigm (3 days during which they received daily intraperitoneal injections of a 20% alcohol/saline solution followed by a 4-day rest period and another binge cycle for 3 consecutive days). At completion of the second binge cycle, mice were subjected to a mid-shaft tibia fracture while intoxicated. Twenty-four hours after the fracture, animals were administered an intravenous transplant of green fluorescent protein-labeled MSC. Two weeks after the fracture, animals were euthanized and injured tibiae were collected and subjected to biomechanical, histologic, and microcomputed tomography analysis.
  
  
  RESULTS
  Pre-injury binge alcohol exposure resulted in a significant impairment in biomechanical strength and decrease in callus volume. MSC transplants restored both fracture callus volume (P < 0.05) and biomechanical strength (P < 0.05) in animals with alcohol-impaired healing. In vivo imaging demonstrated a time-dependent MSC migration to the fracture site.
  
  
  CONCLUSIONS
  These data suggest that a 2-week binge alcohol exposure significantly impairs fracture healing in a murine tibia fracture model. Intravenously administered MSC were capable of specifically homing to the fracture site and of normalizing biomechanical, histologic, and microcomputed tomography parameters of healing in animals exposed to alcohol. Understanding MSC recruitment patterns and functional contributions to fracture repair may lead to their use in patients with impaired fracture healing and nonunion.
authors.affiliation: Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Obermeyer
authors.forename: David
authors.initials: D
authors.lastname: Yonick
authors.forename: Kristen
authors.initials: K
authors.lastname: Lauing
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Stock
authors.forename: Rachel
authors.initials: R
authors.lastname: Nauer
authors.forename: Patrick
authors.initials: P
authors.lastname: Strotman
authors.forename: Ravi
authors.initials: R
authors.lastname: Shankar
authors.forename: Richard
authors.initials: R
authors.lastname: Gamelli
authors.forename: Michael
authors.initials: M
authors.lastname: Stover
authors.forename: John J
authors.initials: JJ
authors.lastname: Callaci
mesh_terms: D000818:Animals; D019245:Compressive Strength; D000431:Ethanol / Q000506:poisoning*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology*; D017759:Fractures, Malunited / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D013718:Tensile Strength; D013978:Tibial Fractures / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D000431:Ethanol