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

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.

Improvement of Rat Spinal Cord Injury Following Lentiviral Vector-Transduced Neural Stem/Progenitor Cells Derived from Human Epileptic Brain Tissue Transplantation with a Self-assembling Peptide Scaffold

“…Increased survival and migration of engrafted hNS/PCs in PM could be due to significantly improved biocompatibility and integration with the host tissue, which promotes the regeneration of damaged spinal cord tissue [24,39]. Hydrogel scaffolds play a shielding role against the host immune system and exhibit anti-gliosis and anti-inflammatory properties when fused with host tissue [42][43][44].…”

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-Ⅰ as an Example

“…Behavioral scoring found that functionalized scaffolds loaded with MSCs enhanced TBI recovery in rats and significantly reduced the numbers of astrocytes and microglia, which release inflammation-related factors after TBI (Figure 3C). Subsequent Western blot analysis also found a reduction in related pro-inflammatory factors, confirming that the combination could improve stem cell survival after transplantation by inhibiting the inflammatory response [53].…”

Mesenchymal stem cell therapy for neurological disorders: The light or the dark side of the force?

“…Even though a variety of bioengineering approaches aiming to facilitate and optimize MSC treatments have emerged throughout the decade, ensuring efficient engraftment and survival of implanted MSCs remains a challenge (Hmadcha et al, 2020b). To address this obstacle, researchers are using biomaterials as scaffolds designed to improve the retention of transplanted cells (Zeng et al, 2015b;Zhang et al, 2018b;Ryu et al, 2019c;Yan et al, 2019;Deng et al, 2020;Sahab Negah et al, 2020;Ma et al, 2021b;Restan Perez et al, 2021). Efforts are being made to produce ideal biodegradable and biocompatible scaffolds based on both synthetic and natural polymers that mirror the biological and mechanical properties of the target tissue (Doblado et al, 2021).…”

“…A study by Negah et al utilized an experimental TBI model in rats to assess whether RADA4GGSIKVAV (R-GSIK), a selfassembling nano-peptide scaffold, brings quantifiable benefits in the form of functional improvement and decrease in neuroinflammation (Sahab Negah et al, 2020). Interestingly, a significant functional recovery was observed in rats that received MSCs with R-GSIK scaffolding, as opposed to those in the control group.…”