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.

中文翻译：

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局灶性脑缺血对人脐带血间充质干细胞单次和两次给药的影响。

在中风的急性期进行干细胞治疗，以保护半组织免受缺血性损伤。然而，在急性期重复细胞治疗的效果仍不清楚。在这项研究中，我们调查并比较了大脑中动脉闭塞后单次（损伤后两天）和重复（损伤后两天和九天）人脐带间充质干细胞（hUCB-MSC）治疗的功能结果（MCAO）。使用旋转脚架和肢体放置测试来研究功能结局，同时通过免疫荧光染色来测量梗死体积和组织损伤，以检查半影区的新血管形成，神经发生，细胞凋亡和炎症。我们观察到明显的运动功能障碍和梗塞的脑容量明显减少，以及与对照组相比，单次和重复hUCB-MSC治疗中神经元和血管的增加。有趣的是，与单药治疗相比，未发现重复给予hUCB-MSC可以引起其他或协同的改善。这项研究表明，对中风后治疗窗口的更清晰了解将促进干细胞治疗临床应用中更有效治疗方案的发展。