Implantation with SHED sheet induced with homogenate protein of spinal cord promotes functional recovery from spinal cord injury in rats

Abstract

Introduction: After spinal cord injury (SCI) occurs, the lesion is in a growth inhibitory microenvironment that severely hinders neural regeneration. In this microenvironment, inhibitory factors are predominant and factors that promote nerve regeneration are few. Improving neurotrophic factors in the microenvironment is the key to treating SCI.Methods: Based on cell sheet technology, we designed a bioactive material with a spinal cord‐like structure –SHED sheet induced with homogenate protein of spinal cord (hp–SHED sheet). Hp–SHED sheet was implanted into the spinal cord lesion for treating SCI rats with SHED suspensions as a control to investigate the effects on nerve regeneration.Results: Hp–SHED sheet revealed a highly porous three–dimensional inner structure, which facilitates nerve cell attachment and migration. Hp-SHED sheet in vivo restored sensory and motor functions in SCI rats by promoting nerve regeneration, axonal remyelination, and inhibiting glial scarring.Discussion: Hp–SHED sheet maximally mimics the microenvironment of the natural spinal cord and facilitate cell survival and differentiation. Hp–SHED sheet could release more neurotrophins and the sustained action of neurotrophins improves the pathological microenvironment, which effectively promotes nerve regeneration, axonal extension, and inhibits glial scarring, thereby promoting the in situ centralis neuroplasticity. Hp–SHED sheet therapy is a promising strategy for effective treatment of SCI based on neurotrophins delivery.

The application of stem cell sheets for neuronal regeneration after spinal cord injury: a systematic review of pre-clinical studies

“…On the 60th day post-SCI, a significantly greater recovery of motor function was observed compared to the control group and SHED suspension group (mean 8.20 ± 0.84 points for the hp-SHED group, mean 6.40 ± 1.14 points for the SHED suspension group, mean 3.20 ± 0.84 points for the control group, p < 0.001 for all comparisons). Similarly, SHED cells induced to differentiate with homogenate proteins of the spinal cord exhibited higher maximum grip strength values compared to all other study groups (mean 235.40 ± 27.93 g for the hp-SHED group, mean 173.00 ± 16.70 g for the SHED suspension group, mean 107.80 ± 14.81 g for the control group, p < 0.05 for all comparisons) [ 25 ]. Another study showed that co-culturing stem cell sheets formed from neuro-induced SHED with undifferentiated SHED resulted in more significant improvements in motor function scores in the grip strength test compared to single-type SHED cell sheets and the control group (mean 11.60 ± 1.14 points for the SHED + iSHED group, mean 7.60 ± 1.14 points for the SHED group, mean 2.60 ± 0.89 points for the control group, p < 0.001 for all comparisons) [ 22 ].…”

“…Following the screening of titles and abstracts of identified articles, 16 articles were included as appropriate for the aim of this systematic review. After the full-text screening, 7 articles which were considered eligible according to inclusion and exclusion criteria, were finally included for qualitative analysis [ 22 , 25 – 30 ]. Nine records might appear to meet the inclusion criteria, but after full-text screening was finally excluded due to the following reasons: in vitro studies (3 articles); test group was cell aggregates (2 articles); non-English study (1 article); conference proceedings (2 articles) and duplicate study (1 article).…”

“…The recovery of motor function was consistently accompanied by sensory function recovery. Three studies evaluated sensory function recovery using the Von Frey test [ 22 , 25 , 28 ]. Among them, two studies utilized a complete spinal cord transection model, which often resulted in severe sensory dysfunction due to the complete disruption of spinal cord conduction pathways [ 22 , 25 ].…”

“…Three studies evaluated sensory function recovery using the Von Frey test [ 22 , 25 , 28 ]. Among them, two studies utilized a complete spinal cord transection model, which often resulted in severe sensory dysfunction due to the complete disruption of spinal cord conduction pathways [ 22 , 25 ]. In this model, rats typically exhibited significant sensory deficits.…”

“…In the complete spinal cord transection model, SHED + iSHED sheets significantly increased the number and proportion of rats showing sensory function recovery compared to the control group, promoting improvements in sensory function (at a total of 20 days after surgery, 100% rats recovered sensation in the SHED + iSHED group, 80% rats recovered sensation in the SHED group, only 20% rats recovered sensation in the control group) [ 22 ], hp-SHED sheets also produced similar results, with 80% of rats recovering sensation in the hp-SHED group compared to 40% in the SHED suspension group and 20% in the control group (a total of 30 days after surgery) [ 25 ].…”