Cell Transplant. 2013;22 Suppl 1:S67-82. doi: 10.3727/096368913X672172. Epub 2013 Sep 10.
Since the brain is naturally inefficient in regenerating functional tissue after injury or disease, novel restorative strategies including stem cell transplantation and tissue engineering have to be considered. We have investigated the use of such strategies in order to achieve better functional repair outcomes. One of the fundamental challenges of successful transplantation is the delivery of cells to the injured site while maintaining cell viability. Classical cell delivery methods of intravenous or intraparenchymal injections are plagued by low engraftment and poor survival of transplanted stem cells. Novel implantable devices such as 3D bioactive scaffolds can provide the physical and metabolic support required for successful progenitor cell engraftment, proliferation, and maturation. In this study, we performed in situ analysis of laminin-linked dextran and gelatin macroporous scaffolds. We revealed the protective action of gelatin-laminin (GL) scaffolds seeded with mesenchymal stem cells derived from donated human Wharton's jelly (hUCMSCs) against neuroinflammatory reactions of injured mammalian brain tissue. These bioscaffolds have been implanted into (i) intact and (ii) ischemic rat hippocampal organotypic slices and into the striatum of (iii) normal and (iv) focally injured brains of adult Wistar rats. We found that transplantation of hUCMSCs encapsulated in GL scaffolds had a significant impact on the prevention of glial scar formation (low glial acidic fibrillary protein) and in the reduction of neuroinflammation (low interleukin-6 and the microglial markers ED1 and Iba1) in the recipient tissue. Moreover, implantation of hUCMSCs encapsulated within GL scaffolds induced matrix metalloproteinase-2 and -9 proteolytic activities in the surrounding brain tissue. This facilitated scaffold biodegradation while leaving the remaining grafted hUCMSCs untouched. In conclusion, transplanting GL scaffolds preseeded with hUCMSCs into mammalian brain tissue escaped the host's immune system and protected neural tissue from neuroinflammatory injury. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.
由于大脑在受伤或患病后自然无法有效地再生功能性组织，因此必须考虑包括干细胞移植和组织工程在内的新型修复策略。我们已经研究了这些策略的使用，以实现更好的功能修复结果。成功移植的一个基本挑战是将细胞递送到损伤部位，同时保持细胞活力。静脉内或脑实质内注射等经典细胞递送方法存在移植干细胞植入率低和存活率差的问题。新型可植入装置，如 3D 生物活性支架，可以为成功的祖细胞植入、增殖和成熟提供所需的物理和代谢支持。在这项研究中，我们对层粘连蛋白连接的右旋糖酐和明胶大孔支架进行了原位分析。我们揭示了由捐赠的人 Wharton 胶（hUCMSCs）衍生的间充质干细胞接种的明胶-层粘连蛋白（GL）支架对受伤哺乳动物脑组织神经炎症反应的保护作用。这些生物支架已被植入到（i）完整的和（ii）缺血的大鼠海马器官型切片中，以及（iii）正常和（iv）局灶性损伤的成年 Wistar 大鼠大脑的纹状体中。我们发现，GL 支架包封的 hUCMSCs 移植对预防神经胶质瘢痕形成（低神经胶质酸性纤维蛋白）和减少神经炎症（低白细胞介素 6 和小胶质细胞标志物 ED1 和 Iba1）有显著影响在受者组织中。此外，GL 支架内包封的 hUCMSCs 的植入诱导了周围脑组织中基质金属蛋白酶-2 和 -9 的蛋白水解活性。这促进了支架的生物降解，同时使剩余的移植 hUCMSCs 不受影响。总之，将 GL 支架预先接种 hUCMSCs 移植到哺乳动物脑组织中可以逃避宿主的免疫系统，并保护神经组织免受神经炎症损伤。本文作为国际神经修复学会（IANR）细胞移植增刊的一部分发表。
