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）：过量的饮酒导致疾病并增加创伤性伤害的风险，对美国的公共卫生负担产生了重大贡献。骨骼是酒精饮料的有害影响的重要目标器官，因为它以两种不同的方式遭受了与酒精有关的损害。直接来自过量饮酒，并且间接是由于饮酒行为引起的创伤损伤的风险增加。断裂非工会是骨断裂损伤通常无法治愈的情况，已经证明需要手术干预，饮酒已被证明会导致这种严重的临床并发症的风险。当前，用于非愈合骨折的PATINT的临床选择，例如自体或去矿物化骨制剂的手术移植，各有局限性。实际上，获得自体骨移植是一种有可能出现另一组并发症的风险的单独的外科手术，而矿化骨骼的制剂是不可靠的。因此，基于干细胞的非工会策略可能会提供一种解决这个具有挑战性的临床问题的新方法。但是，我们目前不了解酒精如何影响干细胞内源性或外源性募集到骨折损伤部位，从而限制了干细胞技术在滥用酒精的患者中的潜力。这项研究的目的是了解骨折损伤后酒精是否影响间充质干细胞募集，以及募集减少是否可能是与酒精相关的抑制骨折损伤修复的基础。由于年轻人更有可能遭受创伤性伤害，因此重要的是要了解周期性或暴饮暴食对骨折修复的影响，因为暴饮暴食是青春期和年轻人种群中饮酒的普遍模式。在住院时，大约40％的骨科住院群体陶醉了，这一事实强调了了解暴饮暴食对骨折修复过程的影响的重要性。我们认为，从本应用中获得的数据将使人们更好地理解为什么饮酒会对断裂修复过程产生负面影响，以及我们如何改善骨质骨折损伤的骨科创伤患者的预后，但通过使用干细胞技术，伴随酒精消耗变得复杂。

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