Kristen Lauing

Publications (14) View all

• Source

  Available from: John J Callaci

  Article: Mesenchymal Stem Cells Facilitate Fracture Repair in an Alcohol-Induced Impaired Healing Model.

  Thomas Obermeyer, David Yonick, Kristen Lauing, Stuart Stock, Rachel Nauer, Patrick Strotman, Ravi Shankar, Richard Gamelli, Michael Stover, John J Callaci
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  ABSTRACT: OBJECTIVES:: 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 MSCs on fracture healing. METHODS:: Bone marrow-derived MSC were isolated from transgenic Green Fluorescent Protein (GFP) C57BL/6 mice and culture expanded using a lineage depletion protocol. Adult wild-type C57BL/6 mice were subjected to a two-week binge alcohol exposure paradigm, (3 days during which they received daily intraperitoneal injections of a 20% alcohol/saline solution followed by a four-day rest period and another 3 consecutive day binge cycle. At completion of the second binge cycle, mice were subjected to a midshaft tibia fracture while intoxicated. Twenty-four hours following fracture, animals were administered an intravenous (IV) transplant of GFP-labeled MSC. Two weeks following fracture, animals were euthanized and injured tibiae were collected and subjected to biomechanical, histologic, and micro-computed 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 two-week binge alcohol exposure significantly impairs fracture healing in a murine tibia fracture model. IV-administered MSC were capable of specifically homing to the fracture site and of normalizing biomechanical, histologic, and microCT 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.
  Journal of orthopaedic trauma 09/2012; · 1.78 Impact Factor
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  Available from: John J Callaci

  Article: Binge alcohol exposure modulates rodent expression of biomarkers of the immunoinflammatory response to orthopaedic trauma.

  Benjamin W Sears, Dustin Volkmer, Sherri Yong, Ryan D Himes, Kristen Lauing, Michelle Morgan, Michael D Stover, John J Callaci
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  ABSTRACT: Alcohol is a known modulator of the immune system and host-defense response. Alcohol abuse is common in trauma patients, although the influence of alcohol intoxication on the inflammatory response following major orthopaedic injury remains unknown. The aim of this investigation was to examine the influence of binge alcohol exposure on biomarkers of the systemic inflammatory response following bilateral traumatic femoral fracture in a rodent model. Ninety-two Sprague-Dawley rats were administered intraperitoneal injections of either saline solution or alcohol for three days. These animals then underwent a sham procedure or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. The animals were killed at specific time points after the injury. Serum and lung tissue were collected, and twenty-five inflammatory markers were analyzed by immunoassay. Histological sections of lung tissue were evaluated by a board-certified pathologist. Bilateral femoral fracture significantly (p < 0.05) increased multiple serum biomarkers of inflammation. Binge alcohol treatment prior to injury significantly suppressed the increase in serum levels of interleukin (IL)-6, white blood cells, IL-2, IL-10, and C-reactive protein after the fracture. However, alcohol-treated animals were found to have increased pulmonary levels of IL-6, IL-1β, IL-2, and macrophage inflammatory protein-1α following bilateral femoral fracture. In addition, lung tissue harvested following alcohol treatment and injury demonstrated increased pathologic changes, including parenchymal, alveolar, and peribronchial leukocyte infiltration and significantly elevated pulmonary wet-to-dry ratio, indicative of pulmonary edema. Our results indicate that acute alcohol intake prior to bilateral femoral fracture with fixation in rats modulates the inflammatory response after injury in a tissue-dependent manner. Although serum biomarkers of inflammation were suppressed in alcohol-treated animals following injury, several measures of pulmonary inflammation including cytokine levels, histological changes, and findings of pulmonary edema were significantly increased following fracture with the presence of alcohol.
  The Journal of Bone and Joint Surgery 04/2011; 93(8):739-49. · 3.27 Impact Factor
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  Available from: Kristen Lauing

  Article: Correlation of measurable serum markers of inflammation with lung levels following bilateral femur fracture in a rat model.

  Benjamin W Sears, Dustin Volkmer, Sherri Yong, Ryan D Himes, Kristen Lauing, Michele Morgan, Michael D Stover, John J Callaci
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  ABSTRACT: INTRODUCTION: Evaluation of the systemic inflammatory status following major orthopedic trauma has become an important adjunct in basing post-injury clinical decisions. In the present study, we examined the correlation of serum and lung inflammatory marker levels following bilateral femur fracture. MATERIALS AND METHODS: 45 Sprague Dawley rats underwent sham operation or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. Animals were euthanized at specific time points after injury. Serum and lung tissue were collected, and 24 inflammatory markers were analyzed by immunoassay. Lung histology was evaluated by a blinded pathologist. RESULTS: Bilateral femur fracture significantly increased serum markers of inflammation including interleukin (IL)-2, IL-6, IL-10, GM-CSF, KC/GRO, MCP-1, and WBC. Femur fracture significantly increased serum and lung levels of IL-1a and KC/GRO at 6 hours. Lung levels of IL-6 demonstrated a trend towards significance. Histologic changes in pulmonary tissue after fracture included pulmonary edema and bone elements including cellular hematopoietic cells, bone fragments and marrow emboli. DISCUSSION AND CONCLUSION: Our results indicate that bilateral femur fracture with fixation in rats results in increases in serum markers of inflammation. Among the inflammatory markers measured, rise in the serum KC/GRO (CINC-1), a homolog to human IL-8, correlated with elevated levels of lung KC/GRO. Ultimately, analysis of serum levels of KC/GRO (CINC-1), or human IL-8, may be a useful adjunct to guide clinical decisions regarding surgical timing.
  Journal of Inflammation Research 08/2010; 2010(3):105-114.
• Source

  Available from: John J Callaci

  Dataset: Long-Term Modulations in the Vertebral Transcriptome of Adolescent-Stage Rats Exposed to Binge Alcohol

  John J Callaci, Ryan Himes, Kristen Lauing, Phillip Roper
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  ABSTRACT: Aims: Dangerous alcohol consumption practices are common in adolescents, yet little is known about their consequences on attainment of peak bone mass and long-term skeletal integrity. We previously demonstrated that binge alcohol-exposed adolescent rats showed site-specific reductions in accruement of bone mineral density and bone strength, which were incompletely recovered following prolonged alcohol abstinence. Currently, we analysed the vertebral transcriptome of adolescent rats following alcohol treat-ment and abstinence to identify long-term molecular changes in the lumbar spine. Methods: Sixty male adolescent Sprague-Dawley rats were assigned to one of six treatment groups receiving binge alcohol (3 g/kg) or saline i.p., 3 consecutive days (acute binge), 4 consecutive weekly (3-day) binge cycles (chronic binge) or 4 weekly binge cycles followed by a 30-day abstinence period (chronic binge with abstinence). Following treatment, lumbar vertebrae were assayed for global transcriptional changes using gene array technology. Results: Analysis of the adolescent rat vertebral transcriptome identified clusters of binge alcohol-sensitive genes display-ing differential expression patterns starting before bone damage was seen and persisting after alcohol treatment was discontinued. Functional grouping of these gene clusters identified candidate cellular pathways affected following acute and chronic binge treatment, as well as pathways remaining modulated following abstinence. Conclusions: These results demonstrate that binge alcohol exposure can produce disruptions of normal bone gene expression patterns in the adolescent rat that persist well beyond the period of active intoxication. This data may have relevance to peak bone mass attainment and future risk of skeletal disease in adolescents engaging in repeated binge-drinking episodes.
• Source

  Available from: John J Callaci

  Dataset: correlation of measurable serum markers of inflammation with lung levels following bilateral femur fracture in a rat model

  Benjamin W Sears, Dustin Volkmer, Sherri Yong, Ryan D Himes, Kristen Lauing, Michele Morgan, Michael D Stover, John J Callaci
  [show abstract] [hide abstract]
  ABSTRACT: Introduction: Evaluation of the systemic inflammatory status following major orthopedic trauma has become an important adjunct in basing post-injury clinical decisions. In the present study, we examined the correlation of serum and lung inflammatory marker levels following bilateral femur fracture. Materials and methods: 45 Sprague Dawley rats underwent sham operation or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. Animals were euthanized at specific time points after injury. Serum and lung tissue were collected, and 24 inflammatory markers were analyzed by immunoassay. Lung histology was evaluated by a blinded pathologist. Results: Bilateral femur fracture significantly increased serum markers of inflammation including interleukin (IL)-2, IL-6, IL-10, GM-CSF, KC/GRO, MCP-1, and WBC. Femur fracture significantly increased serum and lung levels of IL-1a and KC/GRO at 6 hours. Lung levels of IL-6 demonstrated a trend towards significance. Histologic changes in pulmonary tissue after fracture included pulmonary edema and bone elements including cellular hematopoietic cells, bone fragments and marrow emboli. Discussion and conclusion: Our results indicate that bilateral femur fracture with fixation in rats results in increases in serum markers of inflammation. Among the inflammatory markers measured, rise in the serum KC/GRO (CINC-1), a homolog to human IL-8, correlated with elevated levels of lung KC/GRO. Ultimately, analysis of serum levels of KC/GRO (CINC-1), or human IL-8, may be a useful adjunct to guide clinical decisions regarding surgical timing.