Noninvasive Transplantation of Bone Marrow Stromal Cells for Ischemic Stroke: Preliminary Study With a Thermoreversible Gelation Polymer Hydrogel
Noninvasive Transplantation of Bone Marrow Stromal Cells for Ischemic Stroke: Preliminary Study With a Thermoreversible Gelation Polymer Hydrogel
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DOI：
10.1227/01.neu.0000369610.76181.cf
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Iwasaki, Yoshinobu
中科院分区：
文献类型：
--
作者：
Osanai, Toshiya;Kuroda, Satoshi;Iwasaki, Yoshinobu
目的：最近的研究表明，骨髓基质细胞（BMSCs）移植到脑梗死动物模型中具有改善神经功能的潜力。然而，如何移植骨髓间充质干细胞才能安全地获得最有效的治疗效果仍不确定。本研究的目的是评估热可逆凝胶聚合物 (TGP) 水凝胶是否可以作为梗死脑 BMSC 移植中的无创、有价值的支架。 方法：对小鼠进行永久性大脑中动脉闭塞。损伤后7天，将媒介物、BMSC悬浮液或BMSC-TGP构建体移植到同侧完整的新皮质上。在整个实验过程中评估神经系统症状。移植后8周用免疫组织化学检查移植的BMSC的命运。结果：TGP水凝胶完全消失并且在宿主脑中不引起炎症。许多移植细胞广泛植入同侧大脑，包括 BMSC-TGP 构建体处理的小鼠脑梗塞附近的背侧新皮质。它们的数量明显多于 BMSC 治疗的小鼠。大多数 NeuN 和 MAP2 均呈阳性，并在形态上模拟了神经元。结论：研究结果表明，通过手术将组织工程 BMSC 移植到完整的新皮质上，可以增强供体细胞在脑梗塞周围的植入。这些数据可能有助于开发神经组织工程的非侵入性但有效的范例。由于其独特的生化特性，TGP 水凝胶可能成为治疗中枢神经系统疾病的 BMSC 移植中有价值的支架的有前途的候选者。
OBJECTIVE: Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of cerebral infarct. However, it is still undetermined how the BMSCs should be transplanted to obtain the most efficient therapeutic benefits safely. The aim of this study was to assess whether a thermoreversible gelation polymer (TGP) hydrogel acts as a noninvasive, valuable scaffold in BMSC transplantation for infarct brain.METHODS: The mice were subjected to permanent middle cerebral artery occlusion. Vehicle, BMSC suspension, or the BMSC-TGP construct was transplanted onto the ipsilateral intact neocortex at 7 days after the insult. Neurological symptoms were assessed throughout the experiments. The fate of the transplanted BMSC was examined 8 weeks after transplantation with immunohistochemistry.RESULTS: TGP hydrogel completely disappeared and provoked no inflammation in the host brain. Many transplanted cells were widely engrafted in the ipsilateral cerebrum, including the dorsal neocortex adjacent to the cerebral infarct in the BMSC-TGP construct-treated mice. Their number was significantly larger than in the BMSC-treated mice. The majority were positive for both NeuN and MAP2 and morphologically simulated the neurons.CONCLUSION: The findings suggest that surgical transplantation of tissue-engineered BMSCs onto the intact neocortex enhances the engraftment of donor cells around the cerebral infarct. These data may be useful in developing a noninvasive but efficient paradigm in neural tissue engineering. TGP hydrogel can be a promising candidate for valuable scaffolds in BMSC transplantation for central nervous system disorders because of its unique biochemical properties.