Miyamoto Michiyuki, Nakamura Kentaro, Shichinohe Hideo, Yamauchi Tomohiro, Ito Masaki, Saito Hisayasu, Kawabori Masahito, Osanai Toshiya, Sasaki Tasuku, Houkin Kiyohiro, Kuroda Satoshi
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Neurosurgery, Teikyo University Hospital, Tokyo, Japan.
Stem Cells Int. 2018 Apr 8;2018:4829534. doi: 10.1155/2018/4829534. eCollection 2018.
Bone marrow stromal cell (BMSC) transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP) sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo). A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans.
骨髓基质细胞（BMSC）移植对缺血性中风具有治疗潜力。然而，尚不清楚哪种给药途径既能保证安全性又能带来最大的治疗益处。我们评估了一种类似于人胶原蛋白的新型重组肽（RCP）海绵是否能在缺血性中风的细胞治疗中作为一种侵入性较小且有益的支架。培养来自绿色荧光蛋白转基因大鼠的BMSC，并对Sprague-Dawley大鼠进行永久性大脑中动脉闭塞（MCAo）。在MCAo 7天后，将BMSC-RCP海绵构建体移植到同侧完整的新皮质上。将BMSC悬液或赋形剂移植到同侧纹状体中。连续评估大鼠运动功能，并在移植后5周进行组织学分析。结果表明，与赋形剂组相比，BMSC可在RCP海绵中良好增殖，且BMSC-RCP海绵显著促进了功能恢复。组织学分析显示，RCP海绵在宿主脑中引发的炎症反应较少。此外，在BMSC-RCP海绵组中，一些BMSC迁移至梗死周边区域并分化为神经元。这些发现表明RCP海绵可能是人类缺血性中风细胞治疗中无动物蛋白支架的一个有前景的候选者。
