Platelet lysate and granulocyte-colony stimulating factor serve safe and accelerated expansion of human bone marrow stromal cells for stroke therapy.
Platelet lysate and granulocyte-colony stimulating factor serve safe and accelerated expansion of human bone marrow stromal cells for stroke therapy.
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血小板裂解物和粒细胞集落刺激因子可安全、加速地扩增人骨髓基质细胞，用于中风治疗。
DOI：
10.1007/s12975-014-0360-z
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kuroda S.
中科院分区：
文献类型：
--
作者：
Yamauchi T;Saito H;Ito M;Shichinohe H;Houkin K;Kuroda S.
自体人骨髓基质细胞(HBMSCs)应在临床相关时间内，在动物无血清条件下扩增，以确保安全有效的细胞治疗缺血性卒中。本研究旨在评价人骨髓间充质干细胞在血小板裂解物(PL)和粒细胞集落刺激因子(G-CSF)的作用下，是否能增强其在脑梗塞后的增殖能力。人骨髓间充质干细胞在含胎牛血清(FCS)、含PL或含PL/G-CSF的培养液中培养。细胞生长动力学分析。将hBMSCs-PL、hBMSC-PL/G-CSF或赋形剂立体定向植入永久性大脑中动脉闭塞7天大鼠同侧纹状体。术后8周进行运动功能评定，免疫组织化学方法检测移植的hBMSCs的命运。结果表明，hBMSCs-PL/G-CSF比hBMSCs-FCS和hBMSCs-PL有更强的促增殖作用。与赋形剂组相比，用含PL或PL/G-CSF的培养液扩增的hBMSCs移植同样能促进功能恢复。组织学分析显示，hBMSCs-PL和hBMSCs-PL/G-CSF在脑梗塞后的迁移、存活和神经分化方面无明显差异。这些发现有力地表明，联合应用PL和G-CSF可能会加速hBMSC的扩增，并在临床相关的时间段为缺血性中风患者提供安全的细胞治疗。
Autologous human bone marrow stromal cells (hBMSCs) should be expanded in the animal serum-free condition within clinically relevant periods in order to secure safe and effective cell therapy for ischemic stroke. This study was aimed to assess whether the hBMSCs enhance their proliferation capacity and provide beneficial effect in the infarct brain when cultured with platelet lysate (PL) and granulocyte-colony stimulating factor (G-CSF). The hBMSCs were cultured in the fetal calf serum (FCS)-, PL-, or PL/G-CSF-containing medium. Cell growth kinetics was analyzed. The hBMSCs-PL, hBMSC-PL/G-CSF, or vehicle was stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion 7 days after the insult. Motor function was assessed for 8 weeks, and the fate of transplanted hBMSCs was examined using immunohistochemistry. As the results, the hBMSCs-PL/G-CSF showed more enhanced proliferation than the hBMSCs-FCS and hBMSCs-PL. Transplantation of hBMSCs expanded with the PL- or PL/G-CSF-containing medium equally promoted functional recovery compared with the vehicle group. Histological analysis revealed that there were no significant differences in their migration, survival, and neural differentiation in the infarct brain between the hBMSCs-PL and hBMSCs-PL/G-CSF. These findings strongly suggest that the combination of PL and G-CSF may accelerate hBMSC expansion and serve safe cell therapy for patients with ischemic stroke at clinically relevant timing.