Safety/Feasibility of Autologous Mononuclear Bone Marrow Cells in Stroke Patients

自体单核骨髓细胞治疗中风患者的安全性/可行性

• 批准号: 8134133
• 负责人: Sean I Savitz
• 金额: $ 4.03万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-13 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8134133
• 关键词: Acute; Acute Liver Failure; Acute myocardial infarction; Adult; Adult Respiratory Distress Syndrome; Adverse event; Animals; Autologous; Autologous Transplantation; Bone Marrow; Bone Marrow Cells; Brain; Brain Injuries; Brain Mass; Cell Therapy; Cell Transplantation; Cells; Clinical; Clinical Research; Conduct Clinical Trials; Craniocerebral Trauma; Data; Diffusion weighted imaging; Dose; Enrollment; Evaluation; Exploratory/Developmental Grant; Funding; Gait; Grant; Harvest; Hepatic; Hospital safety; Hospitalization; Hospitals; Human; Image; Infarction; Infection; Inflammation; Infusion procedures; Injection of therapeutic agent; Injury; Institution; Intravenous; Intravenous infusion procedures; Ischemic Stroke; Laboratories; Laboratory Study; Liver Failure; Lung; Magnetic Resonance Imaging; Measures; Minority; Modality; Modeling; Monitor; Mononuclear; Myocardial Ischemia; Nature; Neurologic; Outcome; Outcome Measure; Patients; Population; Public Health; Recovery; Research Design; Risk; Rodent; Rodent Model; Safety; Seizures; Series; Severe Adverse Event; Stroke; Symptoms; Testing; Therapeutic; Time; Tissues; Toxic effect; Transplantation; United States National Institutes of Health; Work; acute stroke; body system; design; disability; effective therapy; experience; functional outcomes; improved; indexing; interest; intravenous administration; neurorestoration; novel; novel strategies; novel therapeutic intervention; patient population; phase 1 study; public health relevance; repaired; research study; safety study; stroke recovery

DESCRIPTION (provided by applicant): Cell therapy has emerged as a potential new treatment to reduce injury and improve outcome after ischemic stroke. Several studies have demonstrated that mononuclear cells (MNCs) from bone marrow are safe and enhance recovery in animal stroke models. Our laboratory data indicate that autologous MNCs may reduce inflammation after ischemic stroke in rodents. Our institution has been conducting clinical trials of autologous bone marrow MNCs in patients with ischemic heart disease and head trauma. However, human experience with MNCs in stroke patients is lacking. In this phase I study, we propose to determine the feasibility and safety of bone marrow harvest and intravenous delivery of autologous MNCs in 30 acute ischemic stroke patients. Using the patient's own bone marrow, we will purify and isolate MNCs at an NIH- approved GMP cell therapy facility. Patients with MCA infarcts will receive an IV injection of 10 million MNCs/kg within 24-72 hrs after stroke onset and will be monitored for a range of safety outcomes. Specific Aim 1 is to assess the feasibility of bone marrow harvest and intravenous delivery of MNCs in this patient population. Specific Aim 2 is to perform a comprehensive safety assessment of different organ systems using a battery of clinical, laboratory, and imaging parameters before, during and after the bone marrow harvest and infusion. We will specifically monitor for neurological worsening, acute respiratory distress syndrome, and liver failure. Long term monitoring will continue for 5 years with surveillance brain MRI, neurological evaluations, and laboratory studies. Specific Aim 3 will assess functional outcomes at 90 days using global and modality specific outcome measures. This study would be the first step to assessing the feasibility and safety of intravenous delivery of bone marrow MNCs in acute ischemic stroke, a condition for which there is an enormous public health need for more therapies. PUBLIC HEALTH RELEVANCE: Stroke is the leading cause of adult disability but there are few effective therapies for this devastating condition. Cell therapy is a promising new approach to enhance recovery from stroke. This application proposes to assess the safety and feasibility of autologous bone marrow mononuclear cells in stroke patients. The data from these proposed experiments are essential to begin developing this new therapeutic approach to enhance recovery from stroke.

描述（由申请人提供）：细胞疗法已成为一种潜在的新疗法，可减少缺血性中风后的损伤并改善预后。多项研究表明，来自骨髓的单核细胞 (MNC) 是安全的，并且可以促进动物中风模型的恢复。我们的实验室数据表明，自体 MNC 可以减轻啮齿类动物缺血性中风后的炎症。我们的机构一直在对缺血性心脏病和头部外伤患者进行自体骨髓跨国细胞的临床试验。然而，人类在中风患者中使用跨国公司的经验还很缺乏。在这项 I 期研究中，我们拟确定 30 名急性缺血性中风患者进行骨髓采集和静脉注射自体 MNC 的可行性和安全性。我们将使用患者自己的骨髓，在 NIH 批准的 GMP 细胞治疗设施中纯化和分离 MNC。 MCA 梗塞患者将在中风发作后 24-72 小时内接受 1000 万 MNC/kg 的静脉注射，并监测一系列安全结果。具体目标 1 是评估在该患者群体中采集骨髓和静脉注射 MNC 的可行性。具体目标 2 是在骨髓采集和输注之前、期间和之后使用一系列临床、实验室和成像参数对不同器官系统进行全面的安全评估。我们将特别监测神经系统恶化、急性呼吸窘迫综合征和肝功能衰竭。长期监测将持续 5 年，包括监测脑部 MRI、神经学评估和实验室研究。具体目标 3 将使用整体和特定模式的结果测量来评估 90 天的功能结果。这项研究将是评估急性缺血性中风静脉注射骨髓跨国公司的可行性和安全性的第一步，这种疾病的公共卫生需要更多的治疗方法。 公共卫生相关性：中风是成人残疾的主要原因，但针对这种破坏性疾病的有效治疗方法很少。细胞疗法是一种有前途的促进中风康复的新方法。该申请旨在评估中风患者自体骨髓单核细胞的安全性和可行性。这些拟议实验的数据对于开始开发这种新的治疗方法以促进中风恢复至关重要。