Aggarwal Tanya, Hoeber Jan, Ivert Patrik, Vasylovska Svitlana, Kozlova Elena N
Department of Neuroscience, Uppsala University Biomedical Center, Box 593, 75124, Uppsala, Sweden.
Neurotherapeutics. 2017 Jul;14(3):773-783. doi: 10.1007/s13311-016-0505-8.
ALS is a devastating disease resulting in degeneration of motor neurons (MNs) in the brain and spinal cord. The survival of MNs strongly depends on surrounding glial cells and neurotrophic support from muscles. We previously demonstrated that boundary cap neural crest stem cells (bNCSCs) can give rise to neurons and glial cells in vitro and in vivo and have multiple beneficial effects on co-cultured and co-implanted cells, including neural cells. In this paper, we investigate if bNCSCs may improve survival of MNs harboring a mutant form of human SOD1 (SOD1) in vitro under normal conditions and oxidative stress and in vivo after implantation to the spinal cord. We found that survival of SOD1 MNs in vitro was increased in the presence of bNCSCs under normal conditions as well as under oxidative stress. In addition, when SOD1 MN precursors were implanted to the spinal cord of adult mice, their survival was increased when they were co-implanted with bNCSCs. These findings show that bNCSCs support survival of SOD1 MNs in normal conditions and under oxidative stress in vitro and improve their survival in vivo, suggesting that bNCSCs have a potential for the development of novel stem cell-based therapeutic approaches in ALS models.
肌萎缩侧索硬化症（ALS）是一种毁灭性疾病，会导致大脑和脊髓中的运动神经元（MNs）退化。运动神经元的存活强烈依赖于周围的神经胶质细胞和来自肌肉的神经营养支持。我们之前证明，边界帽神经嵴干细胞（bNCSCs）在体外和体内都能产生神经元和神经胶质细胞，并且对共培养和共植入的细胞（包括神经细胞）有多种有益作用。在本文中，我们研究了bNCSCs在正常条件和氧化应激下体外是否能提高携带人类SOD1突变形式（SOD1）的运动神经元的存活率，以及在植入脊髓后体内是否能提高其存活率。我们发现，在正常条件以及氧化应激下，bNCSCs存在时，体外SOD1运动神经元的存活率会增加。此外，当将SOD1运动神经元前体植入成年小鼠脊髓时，与bNCSCs共植入时它们的存活率会增加。这些发现表明，bNCSCs在正常条件和体外氧化应激下支持SOD1运动神经元的存活，并提高其在体内的存活率，这表明bNCSCs在ALS模型中具有开发新型基于干细胞的治疗方法的潜力。
