Acellular spinal cord scaffold seeded with mesenchymal stem cells promotes long-distance axon regeneration and functional recovery in spinal cord injured rats

Abstract

The stem cell-based experimental therapies are partially successful for the recovery of spinal cord injury (SCI). Recently, acellular spinal cord (ASC) scaffolds which mimic native extracellular matrix (ECM) have been successfully prepared. This study aimed at investigating whether the spinal cord lesion gap could be bridged by implantation of bionic-designed ASC scaffold alone and seeded with human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) respectively, and their effects on functional improvement. A laterally hemisected SCI lesion was performed in adult Sprague-Dawley (SD) rats (n=36) and ASC scaffolds seeded with or without hUCB-MSCs were implanted into the lesion immediately. All rats were behaviorally tested using the Basso-Beattie-Bresnahan (BBB) test once a week for 8weeks. Behavioral analysis showed that there was significant locomotor recovery improvement in combined treatment group (ASC scaffold and ASC scaffold+hUCB-MSCs) as compared with the SCI only group (p<0.01). 5-Bromodeoxyuridine (Brdu)-labeled hUCB-MSCs could also be observed in the implanted ACS scaffold two weeks after implantation. Moreover, host neural cells (mainly oligodendrocytes) were able to migrate into the graft. Biotin-dextran-amine (BDA) tracing test demonstrated that myelinated axons successfully grew into the graft and subsequently promoted axonal regeneration at lesion sites. This study provides evidence for the first time that ASC scaffold seeded with hUCB-MSCs is able to bridge a spinal cord cavity and promote long-distance axon regeneration and functional recovery in SCI rats.