Spinal cord injury (SCI) is a devastating event with huge personal and social costs, for which there is no effective treatment. Cell therapy constitutes a promising therapeutic approach for SCI; however, its clinical potential is seriously limited by their low survival in the hostile conditions encompassing the acute phase of SCI. Human HC016 (hHC016) cells, generated from expanded human adipose mesenchymal stem cells (hAMSCs) and pulsed with a patented protocol with hydrogen peroxide (H2 O2 ), are expected to acquire improved resistance to oxidative environments which appears as a major limiting factor hampering the engrafting success. Our specific aim was to assess whether H2 O2 -pulsed hHC016 cells had an improved survival and thus therapeutic efficacy in a rat contusion model of acute SCI when grafted 48 hr after injury. Functional recovery was evaluated up to 56 days post-injury (dpi) by locomotor (open field test and CatWalk) and sensory (Von Frey and Hargreaves) tests. Besides, histological evaluation of transplanted cell survival and tissue protection/regeneration was also performed. Functional results showed a statistically significant improvement on locomotor recovery outcomes with hHC016 cells. Accordingly, superior cell survival in correlation with long-term neuroprotection, higher axonal regeneration, and reduced astroglial and microglial reactivity was also observed with hHC016 cells. These results demonstrate an enhanced survival capacity of hHC016 cells resulting in improved functional and histological outcomes as compared with hAMSCs, indicating that hHC016 cell transplants may constitute a promising cell therapy for acute SCI.

中文翻译：

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在急性脊髓损伤的大鼠模型中，人类HC016细胞移植物对神经保护和功能恢复的功效。

脊髓损伤（SCI）是具有重大个人和社会成本的毁灭性事件，目前尚无有效的治疗方法。细胞疗法构成了SCI的一种有前途的治疗方法。但是，由于其在包括SCI急性期在内的敌对条件下存活率低，严重限制了其临床潜力。由扩增的人脂肪间充质干细胞（hAMSC）产生并以获得专利的协议用过氧化氢（H2 O2）脉冲处理的人HC016（hHC016）细胞，有望获得对氧化环境的改善抵抗力，这似乎是阻碍人类抗氧化能力的主要限制因素。灌输成功。我们的特定目标是评估在损伤后48小时移植H2 O2脉冲的hHC016细胞在急性SCI大鼠挫伤模型中是否具有提高的存活率并因此具有治疗效果。通过运动（开放式试验和CatWalk）和感官（冯·弗雷和哈格里夫斯）试验评估损伤后长达56天（dpi）的功能恢复。此外，还进行了移植细胞存活和组织保护/再生的组织学评估。功能结果显示，hHC016细胞对运动恢复结果具有统计学上的显着改善。因此，hHC016细胞还观察到与长期神经保护，更高的轴突再生以及减少的星形胶质和小胶质细胞反应性相关的优异细胞存活率。这些结果表明，与hAMSC相比，hHC016细胞的存活能力增强，导致功能和组织学结果改善，表明hHC016细胞移植可能构成急性SCI的有希望的细胞疗法。