Menstrual Blood Cells Display Stem Cell-Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke
Menstrual Blood Cells Display Stem Cell-Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke
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DOI：
10.1089/scd.2009.0340
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发表时间：
2010-04-01
影响因子：
4
通讯作者：
Sanberg, Paul R.
中科院分区：
文献类型：
--
作者：
Borlongan, Cesar V.;Kaneko, Yuji;Sanberg, Paul R.
细胞疗法仍然是神经系统疾病的实验性治疗。追求这种疗法的临床应用的一个主要障碍是找到最佳细胞类型，这将使大量患者群体受益，并发症最少。与移植受体完全匹配的细胞类型似乎是最佳方案。在这里，我们报告月经血可能是自体干细胞的重要来源。培养的月经血的免疫细胞化学测定显示，它们表达胚胎样干细胞表型标记物（Oct 4，SSEA，Nanog），并且当在适当的条件培养基中生长时，表达神经元表型标记物（Nestin，MAP 2）。为了测试这些细胞的治疗潜力，我们使用了氧葡萄糖剥夺（OGD）的体外中风模型，发现与月经血来源的干细胞共培养或暴露于从培养的月经血收集的培养基的OGD暴露的原代大鼠神经元表现出显着减少的细胞死亡。营养因子，如VEGF，BDNF和NT-3，在OGD暴露培养的月经血来源的干细胞的培养基中上调。在成年大鼠中实验性诱导的缺血性卒中后，经血来源的干细胞的移植，无论是脑内还是静脉内，并且没有免疫抑制，与载体输注的大鼠相比，也显著减少了行为和组织学损伤。月经血来源的细胞是一种“个体定制”的供体细胞，至少在女性中完全匹配移植受体。目前移植的月经血来源的细胞所提供的神经结构和行为益处支持它们作为中风细胞治疗的干细胞来源的用途。
Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited significantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of "individually tailored" donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.