Alcohol Effects on SDF1-Mediated Stem Cell Homing Following Bone Fracture Injury

酒精对骨折损伤后 SDF1 介导的干细胞归巢的影响

• 批准号: 8701196
• 负责人: JOHN J. CALLACI
• 金额: $ 17.39万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8701196
• 关键词: Accidents; Admission activity; Adolescent and Young Adult; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Area; Beverages; Bone Injury; Bone Marrow; Bone Transplantation; Bone callus; Categories; Cell Therapy; Chemotactic Factors; Chondrocytes; Clinical; Complication; Country; Data; Disease; Distant; Environment; Fracture; Fracture Healing; Goals; Healed; Heavy Drinking; Homing; Hospitals; Human; In Vitro; Incidence; Inflammatory; Injury; Inpatients; Investigation; Laboratories; Lead; Life; Mediating; Mesenchymal Stem Cells; Modality; Molecular; Morbidity - disease rate; Motor Vehicles; Operative Surgical Procedures; Organ; Orthopedics; Osteoblasts; Osteogenesis; Osteopenia; Outcome; Patients; Pattern; Persons; Phase; Population; Preparation; Process; Public Health; Recruitment Activity; Research; Risk; Risk Factors; Rodent; Signal Transduction; Site; Skeleton; Smoker; Stem cells; Stratification; Stromal Cell-Derived Factor 1; Testing; Time; Tissues; Translational Research; Trauma; United States; Work; Wound Healing; alcohol effect; alcohol exposure; base; binge drinking; bone; bone healing; cell motility; chemokine; clinically significant; diabetic; drinking behavior; healing; improved; in vivo; injured; injury and repair; migration; mortality; novel; novel strategies; osteopontin; osteoprogenitor cell; outcome forecast; programs; public health relevance; repaired; research study; response; skeletal; skeletal injury; stem cell population; stem cell technology; stem cell therapy

DESCRIPTION (provided by applicant): Excessive alcohol consumption resulting in disease and increasing the risk of traumatic injury contributes significantly to the public health burden i the United States. The skeleton is a significant target organ for the deleterious effects of alcoho because it suffers alcohol-related damage in two distinct ways; both directly from excessive alcohol consumption, and indirectly due to the increased risk for traumatic injury caused by alcohol drinking behavior. Fracture non-union is a condition where a bone fracture injury fails to heal normally requiring surgical intervention and alcohol consumption has been shown to contribute to the risk for this serious clinical complication. Currently, clinical options for patints with a non-healing fracture such as surgical grafting of autogenous or de-mineralized bone preparations each have serious limitations. Obtaining autogenous bone graft is effectively a separate surgical procedure at risk for another set complications and de- mineralized bone preparations are unreliable. Thus, stem cell-based strategies for non-union may offer a new approach to resolving this challenging clinical problem. However, we currently do not understand how alcohol affects either endogenous or exogenous recruitment of stem cells to the site of fracture injury, limiting the potential of stem cell technology in alcohol abusing patients. The goal of this investigation is to understand if alcohol affects mesenchymal stem cell recruitment following bone fracture injury and if decreased recruitment may underlie alcohol related inhibition of fracture injury repair. Because young people are more likely to suffer traumatic injury, it is important to understand the effects of periodic or binge drinking on fractue repair as binge alcohol consumption is the prevalent pattern of alcohol drinking in both adolescent and young adult populations. The fact that about 40% of the orthopaedic inpatient population is intoxicated at the time of hospital admission underscores the significance of understanding the impact of binge alcohol consumption on the fracture repair process. We believe that the data obtained from this application will lead to a better understanding of why alcohol consumption negatively impacts the fracture repair process and how we can improve the prognosis for orthopaedic trauma patients with bone fracture injuries complicated by concomitant alcohol consumption though the use of stem cell technology.

描述（由申请人提供）：过量饮酒导致疾病并增加外伤风险，严重加重了美国的公共卫生负担。骨骼是酒精有害影响的重要靶器官，因为它以两种不同的方式遭受酒精相关的损害：直接归因于过量饮酒，间接归因于饮酒行为造成的外伤风险增加。骨折不愈合是指骨折损伤无法正常愈合，需要进行手术干预，并且饮酒已被证明会增加这种严重临床并发症的风险。目前，对于不愈合骨折患者的临床选择，例如自体或脱矿骨制剂的手术移植，均具有严重的局限性。获得自体骨移植实际上是一个单独的外科手术，存在发生其他并发症的风险，并且脱矿骨制剂不可靠。因此，基于干细胞的骨不连策略可能为解决这一具有挑战性的临床问题提供一种新方法。然而，我们目前不了解酒精如何影响干细胞向骨折损伤部位的内源性或外源性募集，从而限制了干细胞技术在酒精滥用患者中的潜力。本研究的目的是了解酒精是否会影响骨折损伤后间充质干细胞的募集，以及募集减少是否可能是酒精相关的骨折损伤修复抑制的基础。由于年轻人更容易遭受创伤，因此了解定期或酗酒对骨折修复的影响非常重要，因为酗酒是青少年和年轻人饮酒的普遍模式。大约 40% 的骨科住院患者在入院时处于醉酒状态，这一事实凸显了了解酗酒对骨折修复过程影响的重要性。我们相信，从该应用程序中获得的数据将有助于更好地理解为什么饮酒会对骨折修复过程产生负面影响，以及如何通过使用干细胞来改善骨科创伤患者的预后。细胞技术。

项目成果

Burn Injury Has Skeletal Site-Specific Effects on Bone Integrity and Markers of Bone Remodeling.

烧伤对骨完整性和骨重塑标志物具有骨骼部位特异性影响。

• DOI: 10.1097/bcr.0000000000000389
• 发表时间: 2016
• 期刊: Journal of burn care & research : official publication of the American Burn Association
• 作者: Hoscheit,Matthew;Conner,Grant;Roemer,James;Vuckovska,Aleksanhdra;Abbasnia,Pegah;Vana,Paul;Shankar,Ravi;Kennedy,Richard;Callaci,John
• 通讯作者: Callaci,John