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

描述（由申请人提供）：细胞疗法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并改善预后。几项研究已经证明，来自骨髓的单核细胞（MNCs）是安全的，并在动物中风模型中促进恢复。我们的实验室数据表明，自体MNCs可以减少啮齿动物缺血性卒中后的炎症。我们的机构一直在缺血性心脏病和头部创伤患者中进行自体骨髓MNC的临床试验。然而，在中风患者中使用MNC的人类经验缺乏。在这项I期研究中，我们计划在30例急性缺血性卒中患者中确定骨髓采集和静脉输注自体MNCs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MNCs。MCA梗死患者将在卒中发作后24-72小时内接受1000万MNC/kg的IV注射，并将监测一系列安全性结局。具体目标1是评估在该患者人群中骨髓采集和静脉内递送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，包括监测脑部MRI、神经系统评价和实验室研究。具体目标3将使用总体和模式特定结局指标评估90天时的功能结局。这项研究将是评估急性缺血性中风患者静脉输注骨髓MNC的可行性和安全性的第一步，这种情况下存在巨大的公共卫生需求，需要更多的治疗。 公共卫生相关性：中风是成人残疾的主要原因，但这种毁灭性的疾病几乎没有有效的治疗方法。细胞疗法是一种很有前途的新方法，以促进中风的恢复。本申请旨在评估自体骨髓单个核细胞在卒中患者中的安全性和可行性。这些实验的数据对于开始开发这种新的治疗方法以促进中风的恢复至关重要。

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.