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

描述（由申请人提供）：细胞治疗已成为一种潜在的新治疗方法，可减少缺血性卒中后的损伤和改善预后。一些研究表明，来自骨髓的单核细胞（MNCs）是安全的，并能促进动物中风模型的恢复。我们的实验室数据表明，自体MNCs可以减轻啮齿动物缺血性中风后的炎症。我院一直在缺血性心脏病和头部外伤患者中开展自体骨髓跨国公司的临床试验。然而，人类在脑卒中患者中治疗跨国公司的经验缺乏。在本一期研究中，我们拟确定30例急性缺血性脑卒中患者骨髓采集和静脉输送自体MNCs的可行性和安全性。使用患者自己的骨髓，我们将在NIH批准的GMP细胞治疗设施中纯化和分离MNCs。中动脉梗死患者将在卒中发作后24-72小时内接受1000万MNCs/kg的静脉注射，并监测一系列安全结果。具体目的1是评估骨髓采集和静脉输送跨国公司在这一患者群体的可行性。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性评估。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MRI、神经学评估和实验室研究。具体目标3将使用全球和模式特定结果测量评估90天的功能结果。这项研究将是评估骨髓跨国公司静脉注射治疗急性缺血性中风的可行性和安全性的第一步，这种情况对更多治疗方法有巨大的公共卫生需求。

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.