gms | German Medical Science

Objective: The pathophysiology of spinal cord injury (SCI) involves post-traumatic inflammation and tissue scarring that interferes with regeneration and recovery. A combined treatment approach with self-assembling peptides (SAP) and neuronal precursor cells (NPC) might improve this inhibitory environment and thus support stem cell survival, differentiation and neuronal regeneration.

Method: Following laminectomy of C6 and C7, Wistar rats were subjected to SCI (clip contusion/compression (28g) model). After randomization in 5 groups (NPC, SAP, NPC+SAP, vehicle, and sham) SAP (QL6) and NPC (400.000 cells) were stereotactically injected into the spinal cord 1 day and 14 days after trauma, respectively. Furthermore, all animals received growth factors (PDGF, EGF, bFGF) subdurally (Alzet micro-pumps) over 7 days and got immunosuppressive therapy (sandimmune and cyclosporine). Prior and post surgery neurological function was assessed on a weekly basis (BBB, incline plane, grip strength, neuropathic pain). 4 weeks after SCI rats were sacrificed and cryosections of the cervical spinal cord were prepared for subsequent immunohistochemical staining.

Results: Referring to the examined part 2.500 μm rostral and caudal from the epicenter of the lesion, animals that were treated with SAP showed a significant larger amount of surviving NPCs (18.088 ± 4.044 vs. 11.493 ± 4.111; n=6; p=0.019) and a facilitated differentiation in neurons (8.7% vs. 5.8%; p=0.015) and oligodendrocytes (11.6% vs. 9.1%; p=0.005). Compared to vehicles or to rats that received only NPCs, animals that were treated with SAPs alone or as a combined approach with SAP and NPCs had smaller intramedullary cysts (p=0.07) and a larger percentage of preserved tissue. In the combined treatment group both astrogliosis (GFAP density) and tissue scaring (CSPG density) were significantly reduced rostral and caudal of the epicenter. Though the total number of motor-neurons (chat pos. cells) was reduced, there was no difference between the groups. Synaptophysin density as a marker for synapto-connectivity, however, was increased both in the NPC and in the combined treatment group. Furthermore, there was an advantage in the behavior assessment favoring the combined treated animals 4 weeks after SCI.

Conclusions: Shaping the inhibitory environment by SAPs reduce astrogliosis and tissue-scarring, support NPC survival and differentiation, and reduce intramedullar cyst formation finally leading to an improved neurological outcome.