Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Transl Stroke Res. 2011 Sep;2(3):294-306. doi: 10.1007/s12975-011-0098-9. Epub 2011 Jul 26.
This study was aimed to test the hypothesis that human bone marrow stromal cells (hBMSC) expanded in fetal calf serum (FCS)-free, platelet lysate (PL)-containing medium would retain their capacity of migration, survival, and neural differentiation when transplanted into the infarct brain, using serial in vivo magnetic resonance imaging (MRI). Cell growth kinetic analysis revealed that hBMSC maintain their proliferative activity when cultured either in conventional FCS-containing medium or FCS-free, PL-containing medium. Subsequently, hBMSC were labeled with a superparamagnetic iron oxide agent and were stereotactically transplanted into the ipsilateral striatum of rats at 7 days after permanent middle cerebral artery occlusion. Serial MRI performed over 8 weeks revealed that they retain their migratory capacity towards the cerebral infarct. Moreover, double fluorescence immunohistochemistry also revealed that they preserve their capacity of differentiation into the neural cells in the peri-infarct area. The hBMSC expanded in the FCS-free, PL-containing medium retain their capacity of migration, survival, and differentiation when stereotactically transplanted into the infarct brain. The present findings strongly suggest the clinical utility of PL as a substitute to expand autologous hBMSC for cerebral infarct in the future.
本研究旨在通过连续的体内磁共振成像(MRI)测试这样一个假设,即在无胎牛血清(FCS)、富含血小板裂解液(PL)的培养基中扩增的人骨髓基质细胞(hBMSC)在移植到梗死脑后,仍能保持其迁移、存活和神经分化的能力。细胞生长动力学分析表明,当在常规含 FCS 的培养基或无 FCS、含 PL 的培养基中培养时,hBMSC 保持其增殖活性。随后,将 hBMSC 用超顺磁氧化铁剂标记,并在永久性大脑中动脉闭塞后 7 天立体定向移植到大鼠同侧纹状体。8 周的连续 MRI 显示它们保持向脑梗死迁移的能力。此外,双重荧光免疫组织化学也显示它们保留了在梗死周围区域分化为神经细胞的能力。在无 FCS、含 PL 的培养基中扩增的 hBMSC 在立体定向移植到梗死脑后,仍能保持其迁移、存活和分化的能力。这些发现强烈提示 PL 作为替代物在未来用于扩增自体 hBMSC 治疗脑梗死的临床应用。