Neurorestorative effect of urinary bladder matrix-mediated neural stem cell transplantation following traumatic brain injury in rats.
Neurorestorative effect of urinary bladder matrix-mediated neural stem cell transplantation following traumatic brain injury in rats.
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DOI：
10.2174/1871527311312030014
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Wang JY;Liou A;Ren ZH;Zhang L;Brown BN;Cui XT;Badylak SF;Cai YN;Guan YQ;Leak RK;Chen J;Ji X;Chen L
创伤性脑损伤（TBI）是年轻人细胞死亡和残疾的主要原因，缺乏成功的治疗策略。TBI的多相损伤严重限制了常规药物治疗的成功。在其他损伤范例中，干细胞在生物活性支架中移植的最新成功为TBI的治疗提供了新的希望。在本研究中，我们将在猪膀胱基质生物活性支架（UBM; 4个注射部位，每个2.5μl）中培养的神经干细胞（0.5×105个细胞/μl）移植到大鼠脑内，然后控制皮质撞击（CCI，速度，4.0 m/sec;持续时间，0.5 sec;深度，3.2 mm）。我们评估了这一策略在对抗运动、记忆和认知能力丧失方面的有效性。移植前，相容性实验表明UBM能够支持神经干细胞的增殖和分化。UBM具有抗炎和体内快速降解的特性，是一种理想的支架材料。移植减少了神经元/组织损失和白色物质损伤，也显著改善了运动、记忆和认知障碍。此外，单独暴露于UBM足以减少TBI的感觉运动技能的丧失（CCI后3-28天检查）。然而，只有含有增殖神经干细胞的UBM有助于减轻记忆和认知障碍（CCI后26-28天检查）。总之，这些结果证明了干细胞在生物活性支架中对TBI的治疗功效，并显示出转化为未来临床应用的前景。
Traumatic brain injury (TBI) is a leading cause of cell death and disability among young adults and lacks a successful therapeutic strategy. The multiphasic injuries of TBI severely limit the success of conventional pharmacological approaches. Recent successes with transplantation of stem cells in bioactive scaffolds in other injury paradigms provide new hope for the treatment of TBI. In this study, we transplanted neural stem cells (0.5×105 cells/μl) cultured in a bioactive scaffold derived from porcine urinary bladder matrix (UBM; 4 injection sites, 2.5μl each) into the rat brain following controlled cortical impact (CCI, velocity, 4.0 m/sec; duration, 0.5 sec; depth, 3.2mm). We evaluated the effectiveness of this strategy to combat the loss of motor, memory and cognitive faculties. Before transplantation, compatibility experiments showed that UBM was able to support extended proliferation and differentiation of neural stem cells. Together with its reported anti-inflammatory properties and rapid degradation characteristics in vivo, UBM emerged to be an ideal scaffold. The transplants reduced neuron/tissue loss and white matter injury, and also significantly ameliorated motor, memory, and cognitive impairments. Furthermore, exposure to UBM alone was sufficient to decrease the loss of sensorimotor skills from TBI (examined 3–28 days post-CCI). However, only UBMs that contained proliferating neural stem cells helped attenuate memory and cognitive impairments (examined 26–28 days post-CCI). In summary, these results demonstrate the therapeutic efficacy of stem cells in bioactive scaffolds against TBI and show promise for translation into future clinical use.
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