Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.

中文翻译：

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在中度和重度脑出血模型中静脉输注人脐带间充质基质细胞。

脑出血（ICH）是威胁生命的疾病，可能发生在年轻人中，通常会导致长期残疾。最近的临床前数据表明，基于间充质基质细胞（MSC）的治疗方法有望将ICH后的脑损伤降至最低。但是，治疗证据和机制见解仍然有限，特别是与其他疾病（例如缺血性中风）相比时。在这里，我们采用了胶原酶诱导的成年大鼠ICH模型，以研究静脉注射人脐带沃顿氏胶冻来源的MSCs（hUC-MSCs）的潜在治疗效果。使用两剂胶原酶可引起中度或严重出血。磁共振成像显示，中度ICH后用hUC-MSCs治疗的动物的血肿残留量小于载体治疗的大鼠，而细胞疗法未能降低重度ICH动物的血肿体积。ICH后长达21天进行了功能评估（旋转架和抬高的身体摇摆测试）。持久性神经功能障碍仅在患有严重ICH的动物中观察到，但细胞疗法并未在功能恢复上引起统计学上的显着改善。还评估了Technetium-99m标记的hUC-MSC的生物分布，表明移植后24小时，在器官（如脾脏和肺）中发现了大多数细胞。不过，有可能检测到大脑中的微弱信号，在患有严重ICH的大鼠的同侧半球中较高。这些数据表明，通过减少残余血肿量，hUC-MSC在大鼠脑出血较轻的情况下具有中等程度的有益作用，并且仍需要优化治疗方法。