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

描述（由申请人提供）：过度饮酒导致疾病并增加创伤性伤害的风险，是美国公共卫生负担的重要因素。骨骼是酒精有害作用的重要靶器官，因为它以两种不同的方式遭受酒精相关损伤；既直接来自过量饮酒，又间接由于饮酒行为造成的创伤性损伤风险增加。骨折不愈合是指骨折损伤不能正常愈合，需要手术干预的一种情况，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，如自体或去矿化骨制剂的手术移植，都有严重的局限性。自体骨移植是一种独立的外科手术，存在其他并发症的风险，而且去矿化骨制剂不可靠。因此，干细胞治疗骨不连可能为解决这一具有挑战性的临床问题提供了一种新的方法。然而，我们目前尚不清楚酒精如何影响内源性或外源性干细胞在骨折损伤部位的募集，这限制了干细胞技术在酗酒患者中的潜力。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。因为年轻人更容易遭受创伤性损伤，所以了解周期性或酗酒对骨折修复的影响是很重要的，因为酗酒是青少年和年轻成年人中普遍存在的饮酒模式。事实上，大约40%的骨科住院患者在入院时是醉酒的，这一事实强调了了解酗酒对骨折修复过程的影响的重要性。我们相信，从这项应用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，以及我们如何通过使用干细胞技术来改善骨折损伤合并饮酒的骨科创伤患者的预后。

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.