Cell Therapy for the Treatment of Acute Respiratory Distress Syndrome

细胞疗法治疗急性呼吸窘迫综合征

• 批准号: 9302927
• 负责人: Mauricio Rojas
• 金额: $ 45万
• 依托单位: ATHERSYS, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302927
• 关键词: Academia; Acute; Acute Lung Injury; Adult Respiratory Distress Syndrome; Allogenic; Alveolar; Animal Model; Animals; Attenuated; Berlin; Bilateral; Biological; Biological Markers; Biotechnology; Blood capillaries; Bone Marrow; Categories; Cell Therapy; Cells; Clinic; Clinical; Clinical Protocols; Clinical Trials; Collaborations; Conduct Clinical Trials; Critical Care; Data; Development; Disease; Dose; Elements; Endotoxins; Enrollment; Gases; Generations; Goals; Health; Heart Atrium; Human; Hypersensitivity; Hypertension; Hypoxemia; Industry; Inflammation; Inflammatory Response; Infusion procedures; Institutes; Intravenous; Investigational Drugs; Investigational New Drug Application; Kidney; Liver; Lung; Measurement; Mesenchymal; Mesenchymal Stem Cells; Modeling; Morbidity - disease rate; Pancreas; Patients; Phase; Phase I Clinical Trials; Physiological; Process; Publishing; Recommendation; Regenerative Medicine; Research Infrastructure; Research Personnel; Role; Safety; Saline; Series; Severities; Sheep; Stem cells; Stromal Cells; Suggestion; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Toxic effect; Translations; Transplantation; Universities; Validation; base; capillary; cell type; clinical application; comparative efficacy; experience; hemodynamics; improved; lung injury; meetings; mortality; mouse model; novel; novel therapeutics; phase I trial; preclinical study; pressure; prevent; protective effect; pulmonary function; repaired; research study

DESCRIPTION (provided by applicant): This is a resubmission of a Phase I-Phase II Fast-Track application for the clinical use of MultiStem in patients with acute respiratory distress syndrome (ARDS). ARDS is defined as acute onset hypoxemia, bilateral radiographic pulmonary infiltrates and lack of atrial pressure hypertension. A novel and exiting possibility is the use of cells as part of the therapy in lung injury. We and other groups have demonstrated that exogenous infusion of isolated mesenchymal stem cells (B-MSC) prevents inflammation and aberrant repair after lung injury. These and other observations suggest that B-MSC is a potentially safe and effective therapeutic intervention in lung injury. Progress toward B-MSC as a cell therapy for ARDS in humans requires completion of preclinical studies and validation in animal models. We propose to evaluate the therapeutic effect of a GMP-produced human adherent bone marrow derived stem cell (MultiStem) in a sheep model of endotoxin-induced moderate-severe ARDS. To our knowledge, there are no published references on the use of this animal model to evaluate the effect of cell therapies for ARDS, making these pre-clinical studies unique and highly novel. This proposal is the result of a close collaboration between the McGowan Institute of Regenerative Medicine, the Division of Pulmonary, Allergy and Critical Care, and the Division of Cardiothoracic Transplantation at the University of Pittsburgh with Athersys, Inc. a biotechnology company specialized in the generation of an allogeneic GMP-grade bone marrow derived adherent stem cells termed MultiStem. We propose that a partnership between academia and industry will accelerate and validate the use of human GMP-produced MultiStem in patients with ARDS. Our groups have the infrastructure and expertise required to assure successful completion of this project. Our goal is to complete the necessary pre-clinical studies required to obtain an Investigational New Drug (IND). Based on a pre-IND meeting with the FDA their suggestions have been incorporated in the present proposal: {Determination of the biological consequences of intrabronchial or intravenous delivery of MultiStem on the sheep model of LPS-induced ARDS}; and Specific Aim 2 (Phase II), to demonstrate the safety of MultiStem in patients with ARDS in a Phase I clinical trial.

描述（由申请人提供）：这是针对急性呼吸窘迫综合征 (ARDS) 患者临床使用 MultiStem 的 I 期 - II 期快速通道申请的重新提交。 ARDS 被定义为急性发作的低氧血症、双侧放射学肺部浸润和缺乏心房压高血压。一种新颖且令人兴奋的可能性是使用细胞作为肺损伤治疗的一部分。我们和其他小组已经证明，分离的间充质干细胞（B-MSC）的外源输注可以预防肺损伤后的炎症和异常修复。这些和其他观察结果表明，B-MSC 是一种潜在安全有效的肺损伤治疗干预措施。 B-MSC 作为人类 ARDS 细胞疗法的进展需要完成临床前研究并在动物模型中进行验证。我们建议在内毒素诱导的中重度 ARDS 绵羊模型中评估 GMP 生产的人贴壁骨髓衍生干细胞 (MultiStem) 的治疗效果。据我们所知，还没有关于使用这种动物模型来评估细胞疗法对 ARDS 效果的公开参考文献，这使得这些临床前研究独特且高度新颖。该提案是匹兹堡大学麦高恩再生医学研究所、肺、过敏和重症监护部门以及心胸移植部门与专门从事再生医学的生物技术公司 Athersys, Inc. 密切合作的结果。一种同种异体 GMP 级骨髓来源的贴壁干细胞，称为 MultiStem。我们建议学术界和工业界之间的合作将加速和验证人类 GMP 生产的 MultiStem 在 ARDS 患者中的使用。我们的团队拥有确保成功完成该项目所需的基础设施和专业知识。我们的目标是完成获得研究性新药 (IND) 所需的必要临床前研究。根据与 FDA 举行的 IND 前会议，他们的建议已纳入本提案中：{确定支气管内或静脉内输送 MultiStem 对 LPS 诱导的 ARDS 绵羊模型的生物学后果}；和具体目标 2（II 期），在 I 期临床试验中证明 MultiStem 对 ARDS 患者的安全性。