Altinova Haktan, Möllers Sven, Deumens Ronald, Gerardo-Nava Jose, Führmann Tobias, van Neerven Sabien Geraldine Antonia, Bozkurt Ahmet, Mueller Christian Andreas, Hoff Hans Joachim, Heschel Ingo, Weis Joachim, Brook Gary Anthony
Department of Neurosurgery, Evangelic Hospital Bethel, Bielefeld, Germany.
2Institute of Neuropathology, Uniklinik RWTH Aachen University, Aachen, Germany.
Tissue Eng Regen Med. 2016 Oct 20;13(5):585-600. doi: 10.1007/s13770-016-9115-0. eCollection 2016 Oct.
The implantation of bioengineered scaffolds into lesion-induced gaps of the spinal cord is a promising strategy for promoting functional tissue repair because it can be combined with other intervention strategies. Our previous investigations showed that functional improvement following the implantation of a longitudinally microstructured collagen scaffold into unilateral mid-cervical spinal cord resection injuries of adult Lewis rats was associated with only poor axon regeneration within the scaffold. In an attempt to improve graft-host integration as well as functional recovery, scaffolds were seeded with highly enriched populations of syngeneic, olfactory bulb-derived ensheathing cells (OECs) prior to implantation into the same lesion model. Regenerating neurofilament-positive axons closely followed the trajectory of the donor OECs, as well as that of the migrating host cells within the scaffold. However, there was only a trend for increased numbers of regenerating axons above that supported by non-seeded scaffolds or in the untreated lesions. Nonetheless, significant functional recovery in skilled forelimb motor function was observed following the implantation of both seeded and non-seeded scaffolds which could not be correlated to the extent of axon regeneration within the scaffold. Mechanisms other than simple bridging of axon regeneration across the lesion must be responsible for the improved motor function.
将生物工程支架植入脊髓损伤诱导的间隙是促进功能性组织修复的一种有前景的策略，因为它可以与其他干预策略相结合。我们之前的研究表明，将纵向微结构化胶原支架植入成年Lewis大鼠单侧颈中段脊髓切除损伤后，功能改善仅与支架内较差的轴突再生有关。为了改善移植物与宿主的整合以及功能恢复，在将支架植入相同损伤模型之前，先接种高度富集的同基因嗅球来源的成鞘细胞（OECs）。再生的神经丝阳性轴突紧密跟随供体OECs以及支架内迁移的宿主细胞的轨迹。然而，再生轴突数量增加的趋势仅比未接种支架或未治疗损伤所支持的数量略有增加。尽管如此，接种和未接种支架植入后均观察到熟练前肢运动功能有显著的功能恢复，这与支架内轴突再生的程度无关。除了简单地在损伤处桥接轴突再生之外，其他机制必定对运动功能的改善起作用。
