Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration.
Background Mesenchymal stem cells (MSCs) display tumour tropism and have been explored as cellular vehicles to deliver anti-cancer agents. As cellular components of the tumour microenvironment, MSCs also influence tumour progression. However, the tumour transformation-related genes of MSCs are not well understood since either oncogenic or tumour suppressor effects within these cells have been reported. Here, we aimed to identify potential biomarkers capable of tumorigenic risk by RNA-seq analysis of human placenta tissue-derived MSCs (hPTMSCs) exposed to the carcinogenic agent 3-methylcholanthrene (3-MC). Results Twenty-nine tumour transformation-related genes and three pluripotency-related genes were identified as differentially expressed genes (DEGs) in hPTMSCs. Importantly, SFRP1 and PTGS2 were further identified as tumour suppressors and oncogenes in hPTMSCs, respectively. The overexpression of SFRP1 and PTGS2 was positively correlated with the expression of the pluripotent markers OCT4, CMYC and NANOG in the human lung adenocarcinoma cell line A549, and the low expression of SFRP1 and PTGS2 was inversely correlated with the expression of the pluripotent markers SOX2, OCT4 and NANOG in hPTMSCs. Interestingly, overexpression of SFRP1 led to reduced cell viability, colony formation and migration of A549 cells. In contrast, the ectopic expression of PTGS2 exerted the opposite effect. Conclusions These results indicate that hPTMSCs with high PTGS2 expression but low SFRP1 expression may have more potential tumorigenic capacity. Taken together, this study suggests that PTGS2 and SFRP1 may be valuable biomarkers for quality and safety control of hPTMSC preparations in clinical applications, which warrants further study.
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