Vishwakarma Sandeep Kumar, Bardia Avinash, Lakkireddy Chandrakala, Paspala Syed Ameer Basha, Khan Aleem Ahmed
Central Laboratory for Stem Cell Research and Translational Medicine, CLRD, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, India.
Dr. Habeebullah Life Sciences, Hyderabad, India.
Front Bioeng Biotechnol. 2018 Nov 1;6:150. doi: 10.3389/fbioe.2018.00150. eCollection 2018.
Spinal cord injury (SCI) is one of the most devastating conditions echoes with inflammation, enhanced fibrosis and larger axonal gaps due to destruction of neurological cells which has caused continuous increasing mortality rate of SCI patients due to absence of suitable treatment modalities. The restoration of structural and functional aspect of damaged neurological tissues at the lesion site in spinal cord has been challenging. Recent developments have showed tremendous potential of neural stem cell-based strategies to form a neuronal relay circuit across the injury gap which facilitates some levels of improvement in SCI condition. However, to provide better therapeutic responses, critical mass of grafted cells must survive for long-term and differentiate into neuronal cells with well-developed axonal networks. Hence, development of tissue specific biological neuronal constructs is highly desirable to provide mechanical and biological support for long-term survival and function of neurological cells within natural biological niche. In this study, we report development of a tissue specific neuronal constructs by culturing human neural precursor cells on decellularized meningeal scaffolds to provide suitable biological neuronal construct which can be used to support mechanical, structural and functional aspect of damaged spinal cord tissues. This particular tissue specific biological construct is immunologically tolerable and provides precisely orchestral three-dimensional platform to choreograph the long-distance axonal guidance and more organized neuronal cell growth. It passes sufficient mechanical and biological properties enriched with several crucial neurotrophins required for long-term survival and function of neurological cells which is required to form proper axonal bridge to regenerate the damaged axonal connectomes at lesion-site in SCI.
脊髓损伤（SCI）是最具毁灭性的病症之一，因神经细胞受损引发炎症、纤维化加剧和轴突间隙增大，由于缺乏合适的治疗方式，SCI患者的死亡率持续上升。在脊髓损伤部位恢复受损神经组织的结构和功能一直具有挑战性。最近的进展表明，基于神经干细胞的策略具有巨大潜力，可在损伤间隙形成神经元中继回路，从而在一定程度上改善SCI病情。然而，为了提供更好的治疗反应，移植细胞的临界数量必须长期存活并分化为具有发达轴突网络的神经元细胞。因此，非常需要开发组织特异性生物神经元构建体，为神经细胞在自然生物微环境中的长期存活和功能提供机械和生物支持。在本研究中，我们报告了通过在脱细胞脑膜支架上培养人神经前体细胞来开发组织特异性神经元构建体，以提供合适的生物神经元构建体，可用于支持受损脊髓组织的机械、结构和功能方面。这种特定的组织特异性生物构建体具有免疫耐受性，并提供精确编排的三维平台，以编排长距离轴突导向和更有序的神经元细胞生长。它具有足够的机械和生物学特性，富含神经细胞长期存活和功能所需的几种关键神经营养因子，这些因子是在SCI损伤部位形成适当的轴突桥以再生受损轴突连接组所必需的。
