Transplantation of Human Neural Stem Cells for Treatment of Chronic SCI

产品说明： 脊髓损伤（SCI）不仅经常损伤传递信号到大脑和从大脑传递信号的白色轴突束，而且损伤中央灰质，导致中间神经元和运动神经元的节段性损失。神经干细胞移植具有替代丢失的神经元和神经胶质的潜力。这些移植的神经元可以在因损伤而断开的脊髓节段之间形成功能中继。这种神经元替代策略对慢性SCI特别有吸引力，慢性SCI具有相对稳定的病变部位，因此对可能有益于急性SCI的神经保护治疗没有反应。我们的初步数据提供了证据，人类神经干细胞可以移植到慢性大鼠挫伤，存活，分化为神经元，并延长轴突突起进入宿主脊髓。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脊髓回路中，并支持导致行为恢复的功能中继。此外，我们将探讨如何康复可以完善这些继电器，以加强行为恢复。这项工作是高度创新和临床导向：1）我们将利用最适用于人类SCI的挫伤型损伤。2)我们将采用从临床上符合要求的人类胚胎干细胞中提取的神经干细胞，这将使临床转化变得容易。3)我们将把联合收割机神经干细胞移植与康复结合起来，这是目前慢性SCI的标准治疗方法。

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.