Axonal remyelination by cord blood stem cells after spinal cord injury
Axonal remyelination by cord blood stem cells after spinal cord injury
复制标题
DOI：
10.1089/neu.2006.0142
复制
发表时间：
2007-02-01
影响因子：
4.2
通讯作者：
Dinh, Dzung H.
中科院分区：
文献类型：
--
作者：
Dasari, Venkata Ramesh;Spomar, Daniel G.;Dinh, Dzung H.
人脐带血干细胞（Human umbilical cord blood stem cells，hUCB）在脊髓损伤（spinal cord injury，SCI）后的治疗修复中具有巨大的潜力。在这里，我们提出了我们的初步调查轴突再生损伤脊髓移植人脐血。使用NYU Impactor使成年雄性大鼠经受中度SCI，并且在SCI后一周将hUCB移植到损伤部位。免疫组织化学数据提供了hUCB分化成几种神经表型的证据，包括神经元、少突胶质细胞和星形胶质细胞。轴突的超微结构分析显示，hUCB在脊髓损伤区的轴突周围形成形态正常的髓鞘。共定位研究证明，来源于hUCB的少突胶质细胞分泌神经营养激素神经营养素-3（NT 3）和脑源性神经营养因子（BDNF）。脐带血干细胞有助于在受损区域合成髓鞘碱性蛋白（MBP）和髓鞘的蛋白脂质蛋白（PLP），从而促进髓鞘再生的过程。通过荧光原位杂交（FISH）分析，在hUCB处理的大鼠中观察到NT 3、BDNF、MBP和PLP的mRNA表达水平升高。基于移植后14天评估的Basso-Beattie-Bresnahan（BBB）评分，hUCB处理的大鼠中后肢运动功能的恢复也显著增强。这些发现表明，hUCB，当移植到脊髓后7天的重量下降损伤，存活至少2周，分化成少突胶质细胞和神经元，并能够改善运动功能。因此，hUCB促进中度SCI后的功能恢复，并可能被证明是一个有用的治疗策略，以修复受损的脊髓。
Human umbilical cord blood stem cells (hUCB) hold great promise for therapeutic repair after spinal cord injury (SCI). Here, we present our preliminary investigations on axonal remyelination of injured spinal cord by transplanted hUCB. Adult male rats were subjected to moderate SCI using NYU Impactor, and hUCB were grafted into the site of injury one week after SCI. Immunohistochemical data provides evidence of differentiation of hUCB into several neural phenotypes including neurons, oligodendrocytes and astrocytes. Ultrastructural analysis of axons reveals that hUCB form morphologically normal appearing myelin sheaths around axons in the injured areas of spinal cord. Colocalization studies prove that oligodendrocytes derived from hUCB secrete neurotrophic hormones neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF). Cord blood stem cells aid in the synthesis of myelin basic protein (MBP) and proteolipid protein (PLP) of myelin in the injured areas, thereby facilitating the process of remyelination. Elevated levels of mRNA expression were observed for NT3, BDNF, MBP and PLP in hUCB-treated rats as revealed by fluorescent in situ hybridization (FISH) analysis. Recovery of hind limb locomotor function was also significantly enhanced in the hUCB-treated rats based on Basso-Beattie-Bresnahan (BBB) scores assessed 14 days after transplantation. These findings demonstrate that hUCB, when transplanted into the spinal cord 7 days after weight-drop injury, survive for at least 2 weeks, differentiate into oligodendrocytes and neurons, and enable improved locomotor function. Therefore, hUCB facilitate functional recovery after moderate SCI and may prove to be a useful therapeutic strategy to repair the injured spinal cord.