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

描述(由申请人提供)：细胞疗法已经成为一种潜在的新疗法，可以减少缺血性中风后的损伤并改善预后。多项研究表明，在动物中风模型中，从骨髓中提取的单个核细胞(MNC)是安全的，并能促进康复。我们的实验室数据表明，自体MNC可以减轻啮齿动物缺血性卒中后的炎症反应。我们机构一直在为缺血性心脏病和脑外伤患者进行自体骨髓单个核细胞的临床试验。然而，在中风患者中缺乏与单核细胞接触的人类经验。在这项I期研究中，我们建议在30名急性缺血性中风患者中确定骨髓采集和静脉输注自体单核细胞的可行性和安全性。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MNC。大脑中动脉梗塞患者将在中风发作后24-72小时内接受1000万MNCs/kg的静脉注射，并将接受一系列安全结果的监测。具体目标1是评估骨髓采集和静脉输注单核细胞在该患者群体中的可行性。具体目标2是在骨髓采集和输注之前、期间和之后使用一组临床、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。我们将专门监测神经恶化、急性呼吸窘迫综合征和肝功能衰竭。长期监测将持续5年，监测脑MRI、神经学评估和实验室研究。具体目标3将使用全球和特定模式的结果衡量标准评估90天后的功能结果。这项研究将是评估静脉注射骨髓单个核细胞治疗急性缺血性中风的可行性和安全性的第一步，对于这种情况，公共卫生需要更多的治疗。 公共卫生相关性：中风是成人残疾的主要原因，但对这种毁灭性的疾病几乎没有有效的治疗方法。细胞疗法是促进中风康复的一种很有前途的新方法。这项应用建议评估中风患者自体骨髓单个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的康复至关重要。

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.