Endothelial Progenitor Cells for Lung Repair

用于肺修复的内皮祖细胞

• 批准号: 7245786
• 负责人: LEWIS H ROMER
• 金额: $ 18.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-02 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7245786
• 关键词: Endothelial; Progenitor; Cells; Lung; Repair

DESCRIPTION (provided by applicant): This 2-year Career Enhancement Award is focused on providing the physician-scientist candidate with new tools and opportunities to accomplish the directed differentiation and optimization of human stem cell populations for use in microvascular restitution. Vascular infrastructure is an essential ingredient for recovery from devastating lung injury, and is integral to the success of tissue engineering efforts. One major challenge to the successful execution of an engineered microvascular network is the lack of a readily usable endothelial cell population. This is an essential ingredient if immunosuppression and graft versus host issues are to be avoided in the already critically ill patients that may receive these engineered networks as a rescue therapy. The two specific aims will focus on the manipulation of signaling pathways and cell cycle control methods in CD14+ peripheral blood mononuclear cells (Aim One) and CD34+ bone marrow stem-progenitor cells (Aim Two) in order to speed directed differentiation to an endothelial phenotype that is optimized for vasculogenesis. This will be accomplished through the use of lentiviral gene transduction. The viability and efficacy of these cells in 3-D matrices derived from human fibroblasts, and in transplantation models in immunodeficient NOD-scid IL2Rg-/- (NOG) mice will be tested. The directed differentiation of human embryonic stem cells to a microvascular endothelial phenotype will also be pursued. These investigations will lay the groundwork for future studies on stem cell populations in tissue-engineered microvascular networks to facilitate new parenchyma! growth following catastrophic pulmonary illness. The sponsor's lab in the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University provides an outstanding training environment for translational stem cell biology. The sponsor's decade of experience as a leader in stem cell research, a first rate team of senior investigators, state-of-the-art equipment, and a mouse transplantation core facility are all made possible by intense and far-sighted institutional commitment to this field of inquiry. PUBLIC HEALTH IMPACT: Life-threatening injury to the lung can destroy normal tissues. The capacity to recuperate depends upon networks of tiny nutrient blood vessels that allow new lung to grow. This Career Enhancement Award will provide special training in stem cells to a physician caring for children with lung injury in the intensive care unit. Using techniques learned in a world-class stem cell center, it may be possible to encourage the development of new blood vessels and increase the pace and success of lung recovery from severe illness.

描述（由申请人提供）：这个为期2年的职业提升奖的重点是为医生科学家候选人提供新的工具和机会，以完成人类干细胞群的定向分化和优化，用于微血管重建。血管基础设施是毁灭性肺损伤恢复的重要组成部分，也是组织工程工作成功不可或缺的一部分。成功实施工程化微血管网络的一个主要挑战是缺乏易于使用的内皮细胞群。这是一个必要的成分，如果免疫抑制和移植物抗宿主问题是要避免在已经危重的患者，可能会接受这些工程网络作为抢救治疗。这两个具体目标将集中在CD 14+外周血单核细胞（目标一）和CD 34+骨髓干祖细胞（目标二）的信号通路和细胞周期控制方法的操纵，以加速定向分化为血管生成优化的内皮表型。这将通过使用慢病毒基因转导来实现。将测试这些细胞在来源于人成纤维细胞的3-D基质中以及在免疫缺陷NOD-scid IL 2 Rg-/-（NOG）小鼠的移植模型中的活力和功效。人胚胎干细胞定向分化为微血管内皮细胞表型也将继续进行。这些研究将为未来组织工程微血管网络中干细胞群的研究奠定基础，以促进新的实质！在灾难性肺病之后的生长。约翰霍普金斯大学Sidney Kimmel综合癌症中心的赞助者实验室为转化干细胞生物学提供了一个出色的培训环境。赞助商作为干细胞研究领导者的十年经验，一流的高级研究人员团队，最先进的设备和小鼠移植核心设施都是通过对该领域调查的强烈和有远见的机构承诺而实现的。对公众健康的影响：危及生命的肺部损伤会破坏正常组织。恢复的能力取决于允许新肺生长的微小营养血管网络。这个职业提升奖将为在重症监护室照顾肺损伤儿童的医生提供干细胞方面的特殊培训。使用在世界一流的干细胞中心学到的技术，有可能鼓励新血管的发育，并提高肺部从严重疾病中恢复的速度和成功率。