Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke
Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke
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DOI：
10.1159/000446404
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发表时间：
2016-01-01
影响因子：
1.9
通讯作者：
Bhatia, Rohit
中科院分区：
文献类型：
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作者：
Bhasin, Ashu;Srivastava, M. V. Padma;Bhatia, Rohit
背景资料：干细胞技术和移植的新兴作用帮助科学家研究它们在神经修复和再生中的潜在作用。干细胞的命运是由它们的生态位决定的，由周围的细胞和分泌的营养生长因子组成。本中期报告通过研究血清血管内皮生长因子（VEGF）和脑源性神经营养生长因子（BDNF）的释放，评价骨髓源性单核干细胞（BM-MNC）治疗慢性缺血性卒中的安全性、可行性和有效性（如有）。研究方法：招募20名中风患者和20名年龄匹配的健康对照者，入选标准如下：距索引事件3个月至1.5年，医学研究理事会（MRC）手部肌肉等级至少为2。Brunnstrom 2-5级意识清醒可以理解他们被随机分配到一组接受自体BM-MNC（平均60-70百万），另一组接受生理盐水输注（安慰剂）。所有患者均接受为期8周的神经运动康复治疗。在基线和8周时进行临床评估[Fugl Meyer量表（FM）、改良Barthel指数（mBI）、MRC分级、Ashworth音调量表]并评估血清VEGF和BDNF水平。结果：研究期间未观察到严重不良事件。两组间无统计学显著性临床改善（FM：95% CI 15.2-5.35，p = 0.25; mBI：95% CI 14.3-4.5，p = 0.31）。与组2相比，发现组1中VEGF和BDNF表达更高（VEGF：442.1对400.3 pg/ml，p = 0.67; BDNF：21.3对19.5 ng/ml），没有任何统计学显著差异。结论：自体骨髓单个核干细胞输注治疗慢性缺血性脑卒中安全、耐受性好。微环境中释放的生长因子（VEGF和BDNF）可能是由于干细胞龛和神经康复机制的旁分泌假说。(C)2016 T he Author（s）Published by S. Karger AG，巴塞尔
Background: The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF). Methods: Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC) grade of hand muscles of at least 2. Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million) and to another group receiving saline infusion (placebo). All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM), modified Barthel index (mBI), MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results: No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31). VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml) with-out any statistically significant difference. Conclusion: Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF) in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime. (C) 2016 T he Author(s) Published by S. Karger AG, Basel