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.
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.
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