Bone Marrow Stromal Cells Combined with a Honeycomb Collagen Sponge Facilitate Neurite Elongation in Vitro and Neural Restoration in the Hemisected Rat Spinal Cord

Abstract

In the last decade, researchers and clinicians have reported that transplantation of bone marrow stromal cells (BMSCs) promotes functional recovery after brain or spinal cord injury (SCI). However, an appropriate scaffold designed for the injured spinal cord is needed to enhance the survival of transplanted BMSCs and to promote nerve regeneration. We previously tested a honeycomb collagen sponge (HC), which when applied to the transected spinal cord allowed bridging of the gap with nerve fibers. In this study, we examined whether the HC implant combined with rat BMSCs increases nerve regeneration in vitro and enhances functional recovery in vivo. We first evaluated the neurite outgrowth of rat dorsal root ganglion (DRG) explants cultured on HC with or without BMSCs in vitro. Regeneration of neurites from the DRGs was increased by BMSCs combined with HC scaffolds. In the in vivo study, 3-mm-long HC scaffolds with or without BMSCs were implanted into the hemisected rat thoracic spinal cord. Four weeks after the procedure, rats implanted with HC scaffolds containing BMSCs displayed better motor and sensory recovery than those implanted with HC scaffolds only. Histologically, more CGRP-positive sensory fibers at the implanted site and 5-HT-positive serotonergic fibers contralateral to the implanted site were observed in spinal cords receiving BMSCs. Furthermore, more rubrospinal neurons projected distally to the HC implant containing BMSCs. Our study indicates that the application of BMSCs in a HC scaffold in the injured spinal cord directly promoted sensory nerve and rubrospinal tract regeneration, thus resulting in functional recovery.

Tubular scaffold with microchannels and an H‐shaped lumen loaded with bone marrow stromal cells promotes neuroregeneration and inhibits apoptosis after spinal cord injury

“…In addition, a small number of 5‐HT 1A + /GFP + or NF‐200 + /GFP + cells and fibres were found in the ST/MC + BMSCs group, especially regenerating 5‐HT 1A + axons, indicating that some BMSCs could differentiate into neurons. The results were similar to those previously reported for the treatment of SCI with BMSC transplantation, which found that human mesenchymal precursor cell transplantation could promote serotonergic or raphespinal axon growth and functional recovery (Hodgetts,Simmons, & Plant ; Mannoji et al, ; Onuma‐Ukegawa et al, ). Significantly increased numbers of 5‐HT 1A + or NF‐200 + axons were observed from 3‐mm rostral to 3‐mm caudal areas within the transected lesion site in the ST/MC + BMSCs group compared with the other three implanted groups.…”

Regenerative Therapies for Spinal Cord Injury

“…9 In a separate study, MSCs combined with a collagen sponge were found to facilitate neurite elongation in a rat model of SCI. 197 In another study, injectable scaffolds made of selfassembling peptide nanofibers containing bone marrow homing, bioactive peptide motifs were described. When combined with human endometrium-derived stromal cells (hEnSCs), these materials were explored for the treatment of experimental chronic SCI in rats.…”

Biomaterial-Supported Cell Transplantation Treatments for Spinal Cord Injury: Challenges and Perspectives

“…Biomaterial scaffolds can fulfill multiple functions for SCI transplantation approaches: (1) specific three-dimensional microarchitectures can be designed with small “chambers” or aligned channels/fibers suited for cell seeding and axonal growth in a directed linear pattern facilitating substantial axonal growth across the lesion for establishment of synaptic connections (Gros et al, 2010 ; Gunther et al, 2015a ; Onuma-Ukegawa et al, 2015 ); (2) serves as a physical matrix for cell adhesion and thereby enhancing survival and retention of grafted cells at the lesion site (Hurtado et al, 2006 ; Olson et al, 2009 ; Bozkurt et al, 2010 ; Park et al, 2012 ) and affect host cell migration (e.g., SCs and astrocytes) (Suzuki et al, 2015 ); (3) influence the behavior of grafted cells and differentiation (Mekhail et al, 2015 ); and (4) control the release of encapsulated bio-active molecules (Mothe et al, 2013 ).…”