Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Cell Biology & Anatomy, New York Medical College, Valhalla, New York, USA.
Stem Cells Transl Med. 2019 Nov;8(11):1157-1169. doi: 10.1002/sctm.19-0082. Epub 2019 Jul 19.
Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH, and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol-induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol-treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1β). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti-inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019;8:1157-1169.
脑室出血（IVH）是早产儿的一种严重并发症，可导致脑积水、脑瘫和智力迟钝。目前尚无治疗 IVH 的方法，标准治疗是支持性护理。来自人脐血的无限制体干细胞（USSCs）在脑和脊髓损伤的动物模型中具有修复作用。将 USSCs 给予患有 IVH 的早产兔幼仔，并评估其对白质完整性和神经行为表现的影响。在甘油诱导的 IVH 后 24 小时，通过脑室内（ICV）或静脉内（IV）途径将 USSCs 注射到 3 天早产（足月 32d）兔幼仔中。幼仔在出生后第 3、7 和 14 天被处死，并将其与甘油处理但未受影响或未处理的对照进行比较。使用体内活体生物发光成像和免疫组织化学分析，与 ICV 相比，在使用 IV 途径时，在第 3 天发现注射的细胞在受伤的实质中，在 ICV 中，细胞被发现靠近脑室壁形成聚集物；我们没有观察到任何来自两种给药途径的不良事件。注射的 USSCs 与减弱的小胶质细胞浸润、较少的细胞凋亡、较少的反应性星形胶质细胞和降低的关键炎症细胞因子（TNFα和 IL1β）水平有关。此外，我们观察到在治疗动物中，髓鞘纤维的保存更好，髓鞘基因表达增加，反应性星形胶质细胞分布改变，这与运动功能的改善有关。总的来说，我们的研究结果支持 USSCs 在受伤的大脑中发挥抗炎作用的可能性，减轻与 IVH 相关的许多不利后果。干细胞转化医学 2019；8：1157-1169。
