Dasari Venkata Ramesh, Spomar Daniel G, Gondi Christopher S, Sloffer Christopher A, Saving Kay L, Gujrati Meena, Rao Jasti S, Dinh Dzung H
Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61605, USA.
J Neurotrauma. 2007 Feb;24(2):391-410. doi: 10.1089/neu.2006.0142.
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.
人脐带血干细胞（hUCB）在脊髓损伤（SCI）后的治疗修复方面具有巨大潜力。在此，我们展示了关于移植hUCB对损伤脊髓进行轴突再髓鞘化的初步研究。成年雄性大鼠使用纽约大学冲击器造成中度脊髓损伤，在脊髓损伤一周后将hUCB移植到损伤部位。免疫组织化学数据提供了hUCB分化为包括神经元、少突胶质细胞和星形胶质细胞在内的多种神经表型的证据。轴突的超微结构分析显示，hUCB在脊髓损伤区域的轴突周围形成形态正常的髓鞘。共定位研究证明，源自hUCB的少突胶质细胞分泌神经营养激素神经营养因子-3（NT3）和脑源性神经营养因子（BDNF）。脐带血干细胞有助于损伤区域髓鞘的髓鞘碱性蛋白（MBP）和蛋白脂蛋白（PLP）的合成，从而促进再髓鞘化过程。荧光原位杂交（FISH）分析显示，hUCB治疗的大鼠中NT3、BDNF、MBP和PLP的mRNA表达水平升高。根据移植后14天评估的Basso-Beattie-Bresnahan（BBB）评分，hUCB治疗的大鼠后肢运动功能的恢复也显著增强。这些发现表明，hUCB在重物坠落损伤7天后移植到脊髓中时，至少存活2周，分化为少突胶质细胞和神经元，并改善运动功能。因此，hUCB促进中度脊髓损伤后的功能恢复，可能被证明是修复损伤脊髓的一种有用治疗策略。
