Transplantation of R-GSIK scaffold with mesenchymal stem cells improves neuroinflammation in a traumatic brain injury model

Sajad Sahab Negah,Ali Gorji,Hassan Hosseini Ravandi,Mohammad Moein Shirzad,Ali Hassani Dooghabadi,Farzin Naseri,Ghazale Biglari

doi:10.1007/s00441-020-03247-0

Abstract

Neural tissue engineering has been introduced as a novel therapeutic strategy for traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs) has been demonstrated to improve functional outcome of brain injury, and RADA4GGSIKVAV (R-GSIK), a self-assembling nano-peptide scaffold, has been suggested to promote the behavior of stem cells. This study was designed to determine the ability of the R-GSIK scaffold in supporting the effects of MSCs on motor function activity and inflammatory responses in an experimental TBI model. A significant recovery of motor function was observed in rats that received MSCs+R-GSIK compared with the control groups. Further analysis showed a reduction in the number of reactive astrocytes and microglial cells in the MSCs and MSCs+R-GSIK groups compared with the control groups. Furthermore, western blot analysis indicated a significant reduction in pro-inflammatory cytokines, such as TLR4, TNF, and IL6, in the MSCs and MSCs+R-GSIK groups compared with the TBI, vehicle, and R-GSIK groups. Overall, this study strengthens the idea that the co-transplantation of MSCs with R-GSIK can increase functional outcomes by preparing a beneficial environment. This improvement may be explained by the immunomodulatory effects of MSCs and the self-assembling nano-scaffold peptide.

Highlights

Traumatic brain injury (TBI) results in a set of secondary pathological alterations within the brain and causes high rates of mortality and disability worldwide (Chauhan 2014; MenonDespite many attempts in the last decades, no definite effective treatment has been identified for traumatic brain injury (TBI) (Skolnick et al 2014; Wright et al 2014)
Our results showed that modified neurological severity score (mNSS) was significantly reduced in the mesenchymal stem cells (MSCs)+R-GSIK group on days 21 and 28 after the treatment compared with the TBI and phosphate buffer saline (PBS) groups (Fig. 2a; P < 0.05)
The time spent in the open arms in the elevated plus maze (EPM) test significantly increased in the MSCs+R-GSIK group compared with the TBI, PBS, and R-GSIK groups (Fig. 2c; P < 0.05)

Summary

Introduction

Traumatic brain injury (TBI) results in a set of secondary pathological alterations within the brain and causes high rates of mortality and disability worldwide (Chauhan 2014; MenonDespite many attempts in the last decades, no definite effective treatment has been identified for TBI (Skolnick et al 2014; Wright et al 2014). RADA16 significantly improved stem cell survival, migration, and differentiation when conjugated with functional motifs (Sahab Negah et al 2019; Shi et al 2016). IKVAV (isoleucine-lysine-valine-alanine-valine), a functional motif of the laminin molecule, improves stem cell survival after transplantation in TBI models (Sahab Negah et al 2018). We developed a biodegradable scaffold containing RADA and IKVAV (RADA16GGSIKVAV; R-GSIK) (Sahab Negah et al 2017). R-GSIK has shown great potential in the improvement of adhesion, proliferation, viability, and differentiation of cells, and stem cells show a greater survival rate when implanted RGSIK scaffold in rats subjected to TBI (Sahab Negah et al 2017, 2019)

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