Long Term Neuroprotective Effects of Human Adipose-Derived Stem Cells in Neonatal Rats Post Hypoxic Ischemic Encephalopathy

Melissa February, Thomas N. Tulenko, Barry Weinberger, Alla Kushnir
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Abstract

Background: Hypoxemic ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in the neonatal population. Recent research has shown human adipose stem cells (hASCs) to have neuroprotective effects in animal models of HIE. This study tested the hypothesis that neurodevelopmental outcomes would be improved using hASC therapy in term neonatal HIE rat model. Methods: Seven day old rats underwent left carotid artery ligation followed by 8% oxygen for 120 minutes, or carotid isolation in shams. Forty-eight hours after surgery half of the rats received hASCs and half normal saline (NS) intravenously. Rota-rod and cylinder tests were used to assess skill learning, balance, coordination, and symmetry of limb use at 2, 4 and 6 weeks of life. Results: HIE rats treated with hASCs traveled further on Rota-rod (p=0.03) when compared to HIE with NS groups. Those in the HIE-hASC group had significant improvement in the usage of the affected limb at week 6 (p=0.03) compared to those with HIE and NS. Rats receiving hASCs post HIE had less cortical atrophy compared to those with HIE and NS. Conclusions: Rats with HIE treated with hASCs showed improvement in long-term neurodevelopmental aspects and decreased cortical atrophy compared to HIE control group.
人脂肪来源干细胞对新生大鼠缺氧缺血性脑病后的长期神经保护作用
背景:低氧缺氧性缺血性脑病(HIE)是新生儿发病率和死亡率的主要原因。最近的研究表明,人脂肪干细胞(hASCs)在HIE动物模型中具有神经保护作用。本研究验证了在足月新生儿HIE大鼠模型中使用hASC治疗可以改善神经发育结局的假设。方法:7日龄大鼠行左颈动脉结扎术,随后8%氧灌注120分钟,或假手术隔离颈动脉。术后48小时,一半大鼠静脉注射hASCs,一半静脉注射生理盐水。在2、4和6周时,采用旋转棒和圆柱体测试来评估技能学习、平衡、协调和肢体使用的对称性。结果:与NS组相比,hASCs组HIE大鼠在Rota-rod上的行走距离更远(p=0.03)。与HIE和NS组相比,HIE- hasc组患者在第6周患肢使用方面有显著改善(p=0.03)。与HIE和NS组相比,HIE后接受hASCs的大鼠皮质萎缩较少。结论:与HIE对照组相比,经hASCs治疗的HIE大鼠在长期神经发育方面有所改善,皮质萎缩减少。
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