Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities.

Recently, mesenchymal stem/stromal cells (MSCs) and their widespread biomedical applications have attracted great consideration from the scientific community around the world. However, reports have shown that the main populations of the transplanted MSCs are trapped in the liver, spleen, and lung upon administration, highlighting the importance of the development of cell-free therapies. Concerning rising evidence suggesting that the beneficial effects of MSC therapy are closely linked to MSC-released components, predominantly MSC-derived exosomes, the development of an MSC-based cell-free approach is of paramount importance. The exosomes are nano-sized (30-100 nm) lipid bilayer membrane vesicles, which are typically released by MSCs and are found in different body fluids. They include various bioactive molecules, such as messenger RNA (mRNA), microRNAs, proteins, and bioactive lipids, thus showing pronounced therapeutic competence for tissues recovery through the maintenance of their endogenous stem cells, the enhancement of regenerative phenotypic traits, inhibition of apoptosis concomitant with immune modulation, and stimulation of the angiogenesis. Conversely, the specific roles of MSC exosomes in the treatment of various tumors remain challenging. The development and clinical application of novel MSC-based cell-free strategies can be supported by better understanding their mechanisms, classifying the subpopulation of exosomes, enhancing the conditions of cell culture and isolation, and increasing the production of exosomes along with engineering exosomes to deliver drugs and therapeutic molecules to the target sites. In the current review, we deliver a brief overview of MSC-derived exosome biogenesis, composition, and isolation methods and discuss recent investigation regarding the therapeutic potential of MSC exosomes in regenerative medicine accompanied by their double-edged sword role in cancer.

Iron Oxide Nanoparticles: Biosynthesis, Magnetic Behavior, Cytotoxic Effect.

Iron oxide nanoparticles have attracted much attention because of their superparamagnetic properties and their potential applications in many fields such as magnetic storage devices, catalysis, sensors, superparamagnetic relaxometry (SPMR), and high-sensitivity biomolecule magnetic resonance imaging (MRI) for medical diagnosis and therapeutics. In this study, iron oxide nanoparticles (Fe2 O3 NPs) have been synthesized using a taranjabin (camelthorn or persian manna) aqueous solution. The synthesized Fe2 O3 NPs were identified through powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), field energy scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX), vibrating-sample magnetometer (VSM) and Raman technics. The results show that the nanoparticles have a hexagonal structure with 20 to 60 nm in size. The cytotoxic effect of the synthesized nanoparticles has been tested upon application against lung cancer cell (A549) lines. It was found that there is no cytotoxic activity at lower concentrations of 200 µg/mL. The ability of the synthesized nanoparticles for lead removal in wastewaters was tested. Results show that highest concentration of adsorbent (50 mg/L) has maximum removal efficiency (96.73 %). So, synthesized Fe2 O3 NPs can be a good candidate to use as heavy metals cleaner from contaminated waters.

Nanoparticles in cancer immunotherapies: An innovative strategy.

Cancer has been one of the most significant causes of mortality, worldwide. Cancer immunotherapy has recently emerged as a competent, cancer-fighting clinical strategy. Nevertheless, due to the difficulty of such treatments, costs, and off-target adverse effects, the implementation of cancer immunotherapy described by the antigen-presenting cell (APC) vaccine and chimeric antigen receptor T cell therapy ex vivo in large clinical trials have been limited. Nowadays, the nanoparticles theranostic system as a promising target-based modality provides new opportunities to improve cancer immunotherapy difficulties and reduce their adverse effects. Meanwhile, the appropriate engineering of nanoparticles taking into consideration nanoparticle characteristics, such as, size, shape, and surface features, as well as the use of these physicochemical properties for suitable biological interactions, provides new possibilities for the application of nanoparticles in cancer immunotherapy. In this review article, we focus on the latest state-of-the-art nanoparticle-based antigen/adjuvant delivery vehicle strategies to professional APCs and engineering specific T lymphocyte required for improving the efficiency of tumor-specific immunotherapy.

Induced pluripotent stem cells (iPSCs) as game-changing tools in the treatment of neurodegenerative disease: Mirage or reality?

Based on investigations, there exist tight correlations between neurodegenerative diseases' incidence and progression and aberrant protein aggregreferates in nervous tissue. However, the pathology of these diseases is not well known, leading to an inability to find an appropriate therapeutic approach to delay occurrence or slow many neurodegenerative diseases' development. The accessibility of induced pluripotent stem cells (iPSCs) in mimicking the phenotypes of various late-onset neurodegenerative diseases presents a novel strategy for in vitro disease modeling. The iPSCs provide a valuable and well-identified resource to clarify neurodegenerative disease mechanisms, as well as prepare a promising human stem cell platform for drug screening. Undoubtedly, neurodegenerative disease modeling using iPSCs has established innovative opportunities for both mechanistic types of research and recognition of novel disease treatments. Most important, the iPSCs have been considered as a novel autologous cell origin for cell-based therapy of neurodegenerative diseases following differentiation to varied types of neural lineage cells (e.g. GABAergic neurons, dopamine neurons, cortical neurons, and motor neurons). In this review, we summarize iPSC-based disease modeling in neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. Moreover, we discuss the efficacy of cell-replacement therapies for neurodegenerative disease.

Hyaluronic acid coated electrospun chitosan-based nanofibers prepared by simultaneous stabilizing and coating.

Chitosan (CS) and hyaluronic acid (HA) are two oppositely charged natural polysaccharides used widely for preparation of nanofibrous scaffolds for tissue engineering applications. Here, we prepared composite fibers composed of CS and HA by electrospinning and subsequent coating. In this regard, two approaches were applied for coating CS nanofibers by HA. In the first method, electrospun nanofiner was first neutralized and then coating was done (HA/CS1), while in the second approach, neutralization and coating were carried out simultaneously (HA/CS2). The overall fibrous structure of the mats was preserved after coating through both methods and there was no remarkable morphological difference between HA/CS1 and HA/CS2 samples. The presence of HA and possible interactions between CS and HA were demonstrated in both HA coated nanofibers by FTIR and thermal gravimetric analysis. However, HA/CS2 nanofibers indicated more interactions between HA and CS. Contact angel measurement revealed differences in the wettability of resultant fibers. Although both scaffolds showed high wettability, the HA/CS2 had lower wettability than HA/CS1. More importantly, there was a difference in cytocompatibility of the scaffolds. Both HA coated scaffolds showed improvement in cell proliferation. However, cell proliferation and adhesion were more when HA was coated through a direct simultaneous method.

Polyethylenimine-based nanocarriers in co-delivery of drug and gene: a developing horizon.

The meaning of gene therapy is the delivery of DNA or RNA to cells for the treatment or prevention of genetic disorders. The success rate of gene therapy depends on the progression and safe gene delivery system. The vectors available for gene therapy are divided into viral and non-viral systems. Viral vectors cause higher transmission efficiency and long gene expression, but they have major problems, such as immunogenicity, carcinogenicity, the inability to transfer large size genes and high costs. Non-viral gene transfer vectors have attracted more attention because they exhibit less toxicity and the ability to transfer large size genes. However, the clinical application of non-viral methods still faces some limitations, including low transmission efficiency and poor gene expression. In recent years, numerous methods and gene-carriers have been developed to improve gene transfer efficiency. The use of Polyethylenimine (PEI) based transfer of collaboration may create a new way of treating diseases and the combination of chemotherapy and gene therapy. The purpose of this paper is to introduce the PEI as an appropriate vector for the effective gene delivery.