Park Hyung Woo, Kim Yona, Chang Jong Wook, Yang Yoon Sun, Oh Wonil, Lee Jae Min, Park Hye Ran, Kim Dong Gyu, Paek Sun Ha
Department of Neurosurgery, Seoul National University College of Medicine, Seoul 03080, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
Stem Cell & Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea.
Exp Neurobiol. 2017 Feb;26(1):55-65. doi: 10.5607/en.2017.26.1.55. Epub 2017 Feb 23.
Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy.
干细胞疗法在中风急性期应用，以保护半暗带组织免受缺血性损伤。然而，急性期重复细胞治疗的效果仍不明确。在本研究中，我们调查并比较了大脑中动脉闭塞（MCAO）后，单次（损伤后两天）和重复（损伤后两天和九天）用人脐带间充质干细胞（hUCB-MSCs）治疗的功能结局。利用转棒试验和肢体放置试验来研究功能结局，而通过免疫荧光染色测量梗死体积和组织损伤，以检测半暗带区域的血管生成、神经发生、细胞凋亡和炎症情况。与对照组相比，我们观察到单次和重复hUCB-MSC治疗均出现明显的运动功能障碍和梗死脑体积显著减小，同时神经元和血管数量增加。有趣的是，未发现重复给予hUCB-MSCs比单一疗法有额外或协同的改善效果。本研究表明，更清楚地了解中风后的治疗窗口将有助于在干细胞治疗的临床应用中制定更有效的治疗方案。
