Department of Neurology, Henry Ford Hospital, 2799 W Grand Boulevard, Detroit, MI 48202, USA.
Stroke. 2011 May;42(5):1437-44. doi: 10.1161/STROKEAHA.110.593129. Epub 2011 Apr 14.
The short time window required by neuroprotective strategies for successful treatment of patients with ischemic stroke precludes treatment for most. However, clinical therapies based on neuroregeneration might extend this therapeutic time window and thus address a significant unmet need. Human umbilical tissue-derived cells have shown great potential as neuroregenerative candidates for stroke treatment.
The effectiveness of intravenous administration of human umbilical tissue-derived cells was tested in a rodent middle cerebral artery stroke model in a dose escalation study (doses tested: 3×10(5), 1×10(6), 3×x10(6), or 1×10(7) cells/injection) followed by a time-of-administration study (time after stroke: Day 1, Day 7, Day 30, and Day 90 at a dose of 5×10(6) cells/injection). Controls were phosphate-buffered saline injections and human bone marrow-derived mesenchymal stromal cell injections. Post-treatment outcome tools included the modified neurological severity score and the adhesive removal tests. Histology was performed on all cases to evaluate synaptogenesis, neurogenesis, angiogenesis, and cell apoptosis.
Statistically significant improvements of human umbilical tissue-derived cell treatment versus phosphate-buffered saline in modified neurological severity scores and adhesive test results were observed for doses≥3×10(6) cells up to 30 days poststroke. At doses≥3×10(6), histological evaluations confirmed enhanced synaptogenesis, vessel density, and reduced apoptosis in the ischemic boundary zone and increased proliferation of progenitor cells in the subventricular zone of human umbilical tissue-derived cell-treated animals versus phosphate-buffered saline controls.
These results indicate effectiveness of intravenous administration of human umbilical tissue-derived cells in a rodent stroke model compared with phosphate-buffered saline control and warrant further investigation for possible use in humans.
神经保护策略治疗缺血性中风患者所需的时间窗口很短，这使得大多数患者无法接受治疗。然而，基于神经再生的临床治疗方法可能会延长这一治疗时间窗口，从而满足重大的未满足需求。人脐带组织来源的细胞已显示出作为中风治疗的神经再生候选物的巨大潜力。
在一个剂量递增研究（测试剂量：3×10(5)、1×10(6)、3×x10(6)或 1×10(7)细胞/注射）中测试了静脉内给予人脐带组织来源细胞的效果，随后进行了给药时间研究（中风后时间：第 1 天、第 7 天、第 30 天和第 90 天，剂量为 5×10(6)细胞/注射）。对照组为磷酸盐缓冲盐水注射和人骨髓间充质基质细胞注射。治疗后的结果评估工具包括改良神经功能缺损评分和粘取试验。对所有病例进行组织学检查，以评估突触形成、神经发生、血管生成和细胞凋亡。
与磷酸盐缓冲盐水相比，剂量≥3×10(6)细胞的人脐带组织来源细胞治疗在改良神经功能缺损评分和粘取试验结果方面均有显著改善，直至中风后 30 天。在剂量≥3×10(6)时，组织学评估证实，与磷酸盐缓冲盐水对照组相比，人脐带组织来源细胞治疗动物的缺血边界区的突触形成、血管密度增加，细胞凋亡减少，室下区的祖细胞增殖增加。
这些结果表明，与磷酸盐缓冲盐水对照相比，静脉内给予人脐带组织来源细胞在大鼠中风模型中是有效的，并值得进一步研究，以探讨其在人类中的可能应用。
