Valdes-Sánchez Teresa, Rodriguez-Jimenez Francisco Javier, García-Cruz Dunia M, Escobar-Ivirico Jorge L, Alastrue-Agudo Ana, Erceg Slaven, Monleón Manuel, Moreno-Manzano Victoria
Neuronal Regeneration Laboratory, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain.
Centre for Biomaterials and Tissue Engineering, Universitat Politècnica de València, Spain.
J Tissue Eng Regen Med. 2015 Jun;9(6):734-9. doi: 10.1002/term.1735. Epub 2013 Mar 27.
Spinal cord injury (SCI) is a cause of paralysis. Although some strategies have been proposed to palliate the severity of this condition, so far no effective therapies have been found to reverse it. Recently, we have shown that acute transplantation of ependymal stem/progenitor cells (epSPCs), which are spinal cord-derived neural precursors, rescue lost neurological function after SCI in rodents. However, in a chronic scenario with axon repulsive reactive scar, cell transplantation alone is not sufficient to bridge a spinal cord lesion, therefore a combinatorial approach is necessary to fill cavities in the damaged tissue with biomaterial that supports stem cells and ensures that better neural integration and survival occur. Caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) is a monomer [obtained as a result of ε-caprolactone and 2-hydroxyethyl methacrylate (HEMA) ring opening/esterification reaction], which can be processed to obtain a porous non-toxic 3D scaffold that shows good biocompatibility with epSPC cultures. epSPCs adhere to the scaffolds and maintain the ability to expand the culture through the biomaterial. However, a significant reduction of cell viability of epSPCs after 6 days in vitro was detected. FM19G11, which has been shown to enhance self-renewal properties, rescues cell viability at 6 days. Moreover, addition of FM19G11 enhances the survival rates of mature neurons from the dorsal root ganglia when cultured with epSPCs on 3D CLMA scaffolds. Overall, CLMA porous scaffolds constitute a good niche to support neural cells for cell transplantation approaches that, in combination with FM19G11, offer a new framework for further trials in spinal cord regeneration.
脊髓损伤(SCI)是导致瘫痪的一个原因。尽管已经提出了一些策略来减轻这种病症的严重程度,但迄今为止尚未找到有效的治疗方法来逆转它。最近,我们已经表明,室管膜干/祖细胞(epSPCs)的急性移植,这些细胞是源自脊髓的神经前体细胞,可挽救啮齿动物脊髓损伤后丧失的神经功能。然而,在具有轴突排斥性反应性瘢痕的慢性情况下,仅细胞移植不足以桥接脊髓损伤,因此需要一种组合方法,用支持干细胞并确保更好的神经整合和存活的生物材料填充受损组织中的空洞。己内酯2 - (甲基丙烯酰氧基)乙酯(CLMA)是一种单体[由ε-己内酯和甲基丙烯酸2 - 羟乙酯(HEMA)的开环/酯化反应得到],它可以被加工成一种多孔无毒的3D支架,该支架与epSPC培养物具有良好的生物相容性。epSPCs附着在支架上,并通过生物材料维持扩大培养的能力。然而,在体外培养6天后检测到epSPCs的细胞活力显著降低。已证明FM19G11可增强自我更新特性,可挽救6天时的细胞活力。此外,当在3D CLMA支架上与epSPCs一起培养时,添加FM19G11可提高背根神经节中成熟神经元的存活率。总体而言,CLMA多孔支架构成了一个良好的生态位,可支持用于细胞移植方法的神经细胞,与FM19G11相结合,为脊髓再生的进一步试验提供了一个新框架。