UFRCC for Cardiovascular Cell Therapy Research Network

描述（由申请人提供）： 本申请的目标有三个方面：更新佛罗里达大学（UF）区域临床中心（UFRCC）的心血管细胞治疗研究网络（CCTRN）;更新成功的研究者培训核心;并申请临床研究协调员技能发展计划。细胞疗法是治疗心血管疾病（CVD）的一个令人兴奋的概念，但尽管有大量的临床前和可行性临床研究，但将研究结果转化为改善患者预后的能力仍然落后。为了满足这一需求，UFRCC利用干细胞生物学/再生医学（T32），骨髓移植中心（NIH/NCI临床研究网络的一部分），新型成像资源，CTSI，高级心力衰竭/移植计划和CV临床试验计划中的既定计划。除了在CCTRN-1中取得的成功外，我们在多中心NHLBI和其他试验测试策略方面也有长期的成功合作记录，以改善心脏灌注或功能并评估临床结局。对于这一更新申请，我们提出，增强祖细胞功能将改善心脏功能，并导致更好的临床结果。我们的第一个方案解决了非STEMI后增强祖细胞归巢。新的特征包括使用岩藻糖基转移酶及其底物（ASC-101）增强与选择素的结合以完成唾液酸化的刘易斯X形成的方法。UFRCC研究人员已经证明ASC-101可以增强血管生成;它已经获得了骨髓移植的孤儿药地位;并且是在UF GMP合规的工厂生产的。第二种方案使用高剂量的新型细胞群（CD 34+）用于患有心力衰竭的CAD患者（如FOCUS）。其他新功能包括：通过暴露于UFRCC研究人员显示的小分子来增加Angl- 7以增强细胞迁移和血管生成;新的递送导管（BioCardia，Helical）;和细胞选择方法（Miltenyi Biotec）。UFRCC的其他独特方面包括与波多黎各大学和行业的合作。这项工作将提高我们对CVD患者细胞治疗作用的理解。

DESCRIPTION (provided by applicant): The objectives of this application are three fold; renew the University of Florida (UF) Regional Clinical Center (UFRCC) for the Cardiovascular Cell Therapy Research Network (CCTRN); renew the successful Investigator Training Core; and apply for the Clinical Research Coordinator Skill Development Program. Cell therapy is an exciting concept for treatment of CV disease (CVD), but despite abundant preclinical and feasibility clinical studies the ability to translate findings to improve patient outcomes has lagged. To address this need, the UFRCC utilizes established programs in Stem Cell Biology/Regenerative Medicine (T32), Bone Marrow Transplant Center (part of NIH/NCI clinical research network), novel imaging resources, the CTSI, Advanced Heart Failure/ Transplant Program, and CV Clinical Trials Program. In addition to success in CCTRN-1, we have a long record of successful collaborations in multicenter NHLBI and other trials testing strategies to improve cardiac perfusion or function and evaluate clinical outcomes. For this renewal application, we propose that enhancing progenitor cell function will improve cardiac function and lead to better clinical outcomes. Our first protocol addresses enhancing progenitor cell homing after non-STEMI. Novel features include a method to enhance binding to selectins using fucosyltransferase and its substrate (ASC-101) to complete sialylated Lewis X formation. UFRCC investigators have shown that ASC-101 enhances vasculogenesis; it has received orphan drug status for bone marrow transplantation; and is manufactured at a UF GMP-compliant facility. The second protocol uses a novel cell population (CD34+) in high dose for CAD patients with heart failure (like FOCUS). Other novel features include: increasing Angl- 7 by exposure to a small molecule shown by UFRCC investigators to enhance cell migration and vasculogenesis; a new delivery catheter (BioCardia, Helical); and cell selection method (Miltenyi Biotec). Additional unique aspects of the UFRCC include collaborations with University of Puerto Rico, and industry. This work will improve our understanding of the role of cell therapy in CVD patients.