Gornicka-Pawlak El Bieta, Janowski Miroslaw, Habich Aleksandra, Jablonska Anna, Drela Katarzyna, Kozlowska Hanna, Lukomska Barbara, Sypecka Joanna, Domanska-Janik Krystyna
NeuroRepair Department, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Acta Neurobiol Exp (Wars). 2011;71(1):46-64. doi: 10.55782/ane-2011-1822.
The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.
本研究的目的是评估在神经转化不同阶段的人脐带血（HUCB）来源细胞动脉内输注的治疗效果。比较了新鲜分离的单核细胞（D-0）、神经定向祖细胞（D-3）和源自脐带血的神经样干细胞（NSC）。通过将哇巴因立体定向注射到背外侧纹状体诱导大鼠局灶性脑损伤。三天后，将10⁷个不同亚群的HUCB细胞注入右颈内动脉。手术后，大鼠饲养在丰富环境中30天。行为评估包括感觉运动缺陷测试（步行梁、转棒、触须诱发前肢放置、阿扑吗啡诱导旋转）、认知障碍（习惯学习和物体识别）和探索行为（旷场试验）。手术后30天测量损伤体积，并在mRNA水平检测大脑中供体细胞的存在。同时，对脑组织进行免疫组织化学分析，以评估哇巴因损伤大鼠的局部组织反应及其在HUCB细胞全身治疗后的调节。不同亚群脐带血细胞的功能效应在各种行为测试中表现出很大差异。进一步分析表明，D-0 HUCB细胞在功能恢复和减少脑损伤体积方面最有效。治疗后30天在大鼠大脑中未检测到任何移植的脐带血来源细胞组分。这可能表明，HUCB来源细胞产生积极作用的机制可能与直接补充神经细胞以外的因素有关。此外，表明局部细胞增殖和迁移的标志物免疫反应性增加，提示通过HUCB D-0细胞动脉内输注刺激内源性修复过程。
