Transplantation of Human Neural Stem Cells for Treatment of Chronic SCI

人类神经干细胞移植治疗慢性脊髓损伤

• 批准号: 9052613
• 负责人: JOHN H. BROCK
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9052613
• 关键词: Achievement; Acute; American; Axon; Behavioral; Brain; California; Caring; Cell Line; Cells; Chronic; Clinical; Clinical Trials; Communities; Contusions; Data; Derivation procedure; Development; Engraftment; Ensure; Esthesia; Extracellular Matrix; Fibrin; Goals; Growth; Health; Healthcare Systems; Human; Implant; Injury; Interneurons; Lead; Lesion; Life; Mediating; Methods; Mission; Modeling; Motor Neurons; Nervous System Trauma; Neuroglia; Neurons; Outcome; Procedures; Process; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Research; Signal Transduction; Site; Spinal; Spinal Cord; Spinal Cord Contusions; Spinal Cord transection injury; Spinal cord injury; Stem cells; Testing; Therapeutic Intervention; Time; Training; Translations; Transplantation; Universities; Veterans; Work; base; central gray matter; clinically relevant; collaborative environment; economic impact; experience; human embryonic stem cell; human stem cells; improved; innovation; loss of function; nerve stem cell; neuronal replacement; neuroprotection; nonhuman primate; novel; novel therapeutics; programs; regenerative therapy; rehabilitation paradigm; relating to nervous system; repaired; research study; standard of care; stem cell biology; stem cell therapy; success; therapy development; white matter

DESCRIPTION: Spinal cord injury (SCI) often damages, not only white matter axon tracts that transmits signals to and from the brain, but also the central gray matter, causing segmental loss of interneurons and motor neurons. Transplantation of neural stem cells has the potential to replace lost neurons and glia. These transplanted neurons can form functional relays between spinal segments disconnected by the injury. This neuronal replacement strategy is particularly appealing for chronic SCI, which has a relatively stable lesion site and thus do not respond to neuroprotection treatments that can potentially benefit acute SCI. Our preliminary data provide evidence that human neural stem cells can be transplanted into the chronic rat contusion, survive, differentiate into neurons, and extend axonal processes into host spinal cord. The proposed studies will determine whether these human stem cells derived from human embryonic stem cells can integrate into rat spinal cord circuitry and support functional relays resulting in behavioral recovery. Furthermore, we will explore how rehabilitation can refine theses relay to enhance behavioral recovery. This work is highly innovative and clinically oriented: 1) We will utilize a contusion type injury that is most applicable to human SCI. 2) We will employ neural stem cells derived from clinically compliant human embryonic stem cells that will ease clinical translation. 3) We will combine neural stem cell grafting with rehabilitation tht is currently the standard of care for chronic SCI.

说明： 脊髓损伤(SCI)不仅损害脑白质轴索，还损害中央灰质，导致中间神经元和运动神经元节段性丢失。神经干细胞移植有可能取代丢失的神经元和神经胶质细胞。这些移植的神经元可以在因损伤而断开连接的脊髓节段之间形成功能继电器。这种神经元替代策略对慢性脊髓损伤特别有吸引力，因为慢性脊髓损伤的病变部位相对稳定，因此对可能有利于急性脊髓损伤的神经保护治疗没有反应。我们的初步数据表明，人类神经干细胞可以移植到慢性大鼠挫伤后存活、分化为神经元，并将轴突延伸到宿主脊髓。这项拟议的研究将确定这些来自人类胚胎干细胞的人类干细胞是否可以整合到大鼠的脊髓回路中，并支持导致行为恢复的功能继电器。此外，我们还将探索康复如何完善这些继电器以促进行为恢复。这项工作具有很高的创新性和临床针对性：1)我们将采用最适用于人类脊髓损伤的挫伤类型。2)我们将使用从符合临床要求的人类胚胎干细胞中提取的神经干细胞，这将使临床移植变得容易。3)我们将神经干细胞移植与康复相结合，这是目前慢性脊髓损伤的治疗标准。