Brain tumors are one of the most mortal cancers, leading to many deaths among kids and adults. Surgery, chemotherapy, and radiotherapy are available options for brain tumor treatment. However, these methods are not able to eradicate cancer cells. The blood–brain barrier (BBB) is one of the most important barriers to treat brain tumors that prevents adequate drug delivery to brain tissue. The connection between different brain parts is heterogeneous and causes many challenges in treatment. Mesenchymal stem cells (MSCs) migrate to brain tumor cells and have anti-tumor effects by delivering cytotoxic compounds. They contain very high regenerative properties, as well as support the immune system. MSCs-based therapy involves cell replacement and releases various vesicles, including exosomes. Exosomes receive more attention due to their excellent stability, less immunogenicity and toxicity compare to cells. Exosomes derived from MSCs can develop a powerful therapeutic strategy for different diseases and be a hopeful candidate for cell-based and cell-free regenerative medicine. These nanoparticles contain nucleic acid, proteins, lipids, microRNAs, and other biologically active substances. Many studies show that each microRNA can prevent angiogenesis, migration, and metastasis in glioblastoma. These exosomes can—act as a suitable nanoparticle carrier for therapeutic applications of brain tumors by passing through the BBB. In this review, we discuss potential applications of MSC and their produced exosomes in the treatment of brain tumors.
1 September 2015 in Journal of Biomaterials Science, Polymer Edition
The aim of this study was to develop nanofibrous silk substrates for limbal stem cell expansion that can serve as a potential alternative substrate to replace human amniotic membrane. The human limbal stem cell was used to evaluate the biocompatibility of substrates (random and oriented nanofibrous mats, and human amniotic membrane) based on their phenotypic profile, viability, proliferation, and attachment ability. Biocompatibility results indicated that all substrates were highly biocompatible, as limbal stem cells could favorably attach and proliferate on the nanofibrous surfaces. Microscopic figures showed that the human limbal stem cells were firmly anchored to the substrates and were able to retain a normal corneal stem cell phenotype. Microscopic analyses illustrated that cells infiltrated the nanofibers and successfully formed a three-dimensional corneal epithelium, which was viable for 15 days. Immunocytochemistry and real-time PCR results revealed no change in the expression profile of limbal stem cells grown on nanofibrous substrates when compared to those grown on human amniotic membrane. In addition, electrospun nanofibrous silk substrates especially oriented mat provides not only a milieu supporting limbal stem cells expansion, but also serve as a useful alternative carrier for ocular surface tissue engineering and could be used as an alternative substrate to amniotic membrane.
The aim of this study was to produce a chitosan–cross-linked nanofibrous biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit. The artificial nerve scaffold designed by electrospinning method and cross-linked with chitosan by chemical method. Afterwards, the scaffolds were evaluated by microscopic, physical, and mechanical analyses and cell culture assays with Schwann cells. The conduits were implanted into a 10 mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently good mechanical properties to serve as a nerve guide. Cellular experiments showed a better cell adhesion, growth, and proliferation inside the cross-linked nanofibrous scaffolds compared with un–cross-linked ones, also Schwann cells well attached on chitosan–cross-linked nanofibrous surface. The in vivo results demonstrated that in the nanofibrous graft, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. This neural conduit appears to have the right organization for testing in vivo nerve tissue engineering studies.
A nanofibrous PHBV nerve conduit has been used to evaluate its efficiency based on the promotion of nerve regeneration in rats. The designed conduits were investigated by physical, mechanical and microscopic analyses. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently high mechanical properties to serve as a nerve guide. The results demonstrated that in the nanofibrous graft with cells, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. For the grafts especially the nanofibrous conduits with cells, muscle cells of gastrocnemius on the operated side were uniform in their size and structures. This study proves the feasibility of artificial conduit with Schwann cells for nerve regeneration by bridging a longer defect in a rat model.