Rodent Neural Progenitor Cells Support Functional Recovery after Cervical Spinal Cord Contusion

Abstract

Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p < 0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.

Adult Neural Progenitor Cells Transplanted into Spinal Cord Injury Differentiate into Oligodendrocytes, Enhance Myelination, and Contribute to Recovery

“…Our findings, indicating that transplanted NPCs have the potential to differentiate into all major cell types in the CNS, reflects what Boido et al. (2011) and others also found to be true for transplanted NPCs (Boido et al., 2011, Brock et al., 2017, Hong et al., 2014). However, our data are more in line with reports indicating that glial cell differentiation is more prevalent than differentiation into neural cells (Karimi-Abdolrezaee et al., 2006, Macias et al., 2006, Mligiliche et al., 2005, Pallini et al., 2005, Parr et al., 2007, Pfeifer et al., 2004, Pfeifer et al., 2006, Piltti et al., 2013, Ricci-Vitiani et al., 2006, Salewski et al., 2015, Sandhu et al., 2017, Vroemen et al., 2003).…”

“…Conflicting results concerning the differentiation potential of transplanted NPCs have been reported. While differentiation into all neural lineages has been observed (Boido et al., 2011, Brock et al., 2017, Hong et al., 2014), some authors could only detect differentiation into astrocytes (Macias et al., 2006, Mligiliche et al., 2005, Pallini et al., 2005, Ricci-Vitiani et al., 2006, Sandhu et al., 2017). Specific differentiation into glia but not neurons has also been described (Karimi-Abdolrezaee et al., 2006, Parr et al., 2007, Pfeifer et al., 2004, Pfeifer et al., 2006, Piltti et al., 2013, Salewski et al., 2015, Vroemen et al., 2003).…”

Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

“…Therefore, the choice of the SCI model apparently exerts a great impact on the fate outcome, which could indeed influence the degree of cellular and functional regeneration. Nevertheless, there are always exceptions to the rule where environmental influences are not dominating [80,82,100,101]. Transplantation of fetal rat spinal cord NSCs into an adult rat SCI compression model resulted in a majority of GFAP-positive astrocytes (32.6%), a few 2′,3′-cyclic nucleotide 3′ phosphodiesterase- (CNP) positive oligodendrocytes (4.4%) and low degree of neuronal cells (5.9%) whereas precursor marker expression (such as neuronal Dcx or oligodendroglial NG2) was not investigated [80].…”

Transplanting Cells for Spinal Cord Repair: Who, What, When, Where and Why?

“…With this in mind, recent studies have begun to focus on subsets of these SpINs for transplantation 21 , to assess which cells may be most effective for repair. The V2a SpINs have been a strong candidate for repair of motor networks [21][22][23][24] . In the uninjured spinal cord, it is a pre-motor, excitatory SpIN that projects ipsilaterally.…”