Transplantation of Umbilical Cord Blood Stem Cells in Ischemic Brain Injury

脐带血干细胞移植治疗缺血性脑损伤

• 批准号: 7481592
• 负责人: Nicole A Kuzmin-Nichols
• 金额: $ 9.63万
• 依托单位: SANERON CCEL THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7481592
• 关键词: Aging; Animals; Astrocytes; Behavior; Blood; Blood Vessels; Bone Marrow Cells; Brain; Brain Injuries; Bromodeoxyuridine; CD34 gene; Cell Count; Cell Nucleus; Cell Transplantation; Cell Transplants; Cells; Cessation of life; Characteristics; Clinical; Cord Blood Stem Cell Transplantation; Country; Development; Disease; Dose; Drug usage; Event; Exhibits; Experimental Models; Future; Glial Fibrillary Acidic Protein; Hematopoietic; Hematopoietic stem cells; Hour; Human; Image; Immune system; Immunohistochemistry; Infarction; Injury; Ischemia; Ischemic Brain Injury; Ischemic Stroke; Label; Lesion; Literature; Magnetic Resonance; Magnetic Resonance Imaging; Metabolic; Methods; Middle Cerebral Artery Occlusion; Monitor; Mononuclear; Nervous System Physiology; Neuraxis; Neurologic; Neurons; Nude Rats; Numbers; Oligodendroglia; Organ; PECAM1 gene; Patients; Phase; Population; Protocols documentation; Public Health; Purpose; Range; Rattus; Reporting; Rodent; Rodent Model; Small Business Technology Transfer Research; Source; Spectrum Analysis; Stem cell transplant; Stem cells; Stroke; Testing; Therapeutic; Time; Tissues; Translating; Transplantation; Umbilical Cord Blood; Umbilical cord structure; base; behavior test; brain tissue; day; disability; functional restoration; hemodynamics; in vivo; intravenous administration; ischemic lesion; neovascularization; neurogenesis; novel; novel strategies; relating to nervous system; repaired; research study; response; scale up; self-renewal; size; stem cell therapy; tissue processing

DESCRIPTION (provided by applicant): Human umbilical cord blood is a rich source of hematopoietic stem cells that can be used to re-populate the blood and immune systems. In preliminary studies we have identified a novel population of non-hematopoietic cells that exhibit extensive self-renewal and markers characteristic of stem cells. We postulate that these cells can be used to repair the brain following ischemic injury. In specific aim 1 we will conduct studies to compare high vs. low passage stem cells to determine whether high passage cells can repair the brain and restore function in a rodent model of experimental stroke. In specific aim 2 we will conduct cell dose-response experiments to determine an optimal range in the number of stem cells that minimizes neurological and neuropathological deficits. Behavioral tests and novel magnetic resonance protocols will be used to assess neurological function. In specific aim 3, the ability of the transplanted cells to differentiate into neural cells will be assessed by immunohistochemistry. The ability of the grafted cells to induce neurogenesis and vascular neogenesis will also be assessed. The results from this study will provide information on whether non- hematopoietic cord blood stem cells can be used as a therapy for treating ischemic brain injury. PUBLIC HEALTH RELEVANCE: Stroke resulting from ischemic brain injury is a major cause of disability and death in this country. At the present time drugs that are used to treat ischemic stroke must be administered within 3 hours after the ischemic event in order to be effective. We have discovered a unique population of umbilical cord stem cells that appear to reduce the size of lesions in the brain that result from experimental ischemia and minimize the extent of neurological deficits even when administered 48 hours after the stroke. Our proposed project intends to determine whether these cells can be developed as a therapy for treating patients who have suffered ischemic injuries to the brain.

描述（由申请人提供）：人类脐带血是造血干细胞的丰富来源，可用于重新填充血液和免疫系统。在初步研究中，我们已经确定了一种新的非造血细胞群，它们表现出广泛的自我更新和干细胞特征的标记。我们假设这些细胞可以用来修复缺血性脑损伤。在具体目标1中，我们将进行研究，比较高传代和低传代干细胞，以确定高传代细胞是否可以修复大脑并恢复实验性中风啮齿动物模型的功能。在具体目标2中，我们将进行细胞剂量反应实验，以确定干细胞数量的最佳范围，从而最大限度地减少神经和神经病理缺陷。行为测试和新的磁共振协议将用于评估神经功能。在特定目的3中，移植细胞向神经细胞分化的能力将通过免疫组织化学来评估。移植细胞诱导神经发生和血管新生的能力也将被评估。本研究的结果将为非造血脐带血干细胞是否可用于缺血性脑损伤的治疗提供信息。公共卫生相关性：缺血性脑损伤引起的中风是美国致残和死亡的主要原因。目前用于治疗缺血性脑卒中的药物必须在缺血事件发生后3小时内给药才能有效。我们已经发现了一种独特的脐带干细胞群，它似乎可以减少由实验性缺血引起的大脑损伤的大小，并且即使在中风后48小时给药，也可以最大限度地减少神经功能缺损的程度。我们提出的项目旨在确定这些细胞是否可以发展为治疗脑缺血性损伤患者的疗法。