The advancement of natural-based biomaterials in providing a carrier has revealed a wide range of benefits in the biomedical sciences, particularly in wound healing, tissue engineering and regenerative medicine. Incorporating nanoparticles within polymer composites has been reported to enhance scaffolding performance, cellular interactions and their physico-chemical and biological properties in comparison to analogue composites without nanoparticles. This review summarized the current knowledge of nanoparticles incorporated into natural-based biomaterials with effects on their cellular interactions in wound healing. Although the mechanisms of wound healing and the function of specific cells in wound repair have been partially described, many of the underlying signaling pathways remain unknown. We also reviewed the current understanding and new insights into the wingless/integrated (Wnt)/β-catenin pathway and other signaling pathways of transforming growth factor beta (TGF-β), Notch, and Sonic hedgehog during wound healing. The findings demonstrated that most of the studies reported positive outcomes of biomaterial scaffolds incorporated with nanoparticles on cell attachment, viability, proliferation, and migration. Combining therapies consisting of nanoparticles and biomaterials could be promising for future therapies and better outcomes in tissue engineering and regenerative medicine.
In the field of cell-based therapy and regenerative medicine, clinical application is the ultimate goal. However, one major concern is: does in vitro manipulation during culture expansion increases tumourigenicity risk on the prepared cells? Therefore, the aim of this study was to investigate the effect of long-term in vitro expansion on human adipose-derived stem cells (ASCs). The ASCs were harvested from lipo-aspirate samples and cultured until passage 20 (P20), using standard culture procedures. ASCs at P5, P10, P15 and P20 were analysed for morphological changes, DNA damage (Comet assay), tumour suppressor gene expression level (quantitative PCR), p53 mutation, telomerase activity, telomere length determination and in vivo tumourigenicity test. Our data showed that ASCs lost their fibroblastic feature in long-term culture. The population doubling time of ASCs increased with long-term culture especially at P15 and P20. There was an increase in DNA damage at later passages (P15 and P20). No significant changes were observed in both p53 and p21 genes expression throughout the long-term culture. There was also no p53 mutation detected and no significant changes were recorded in the relative telomerase activity (RTA) and mean telomere length (TRF) in ASCs at all passages. In vivo implantation of ASCs at P15 and P20 into the nude mice did not result in tumour formation after 4 months. The data showed that ASCs have low risk of tumourigenicity up to P20, with a total population doubling of 42 times. This indicates that adipose tissue should be a safe source of stem cells for cell-based therapy.
The rapid mutation of the SARS-CoV-2 virus is now a major concern with no effective drugs and treatments. The severity of the disease is linked to the induction of a cytokine storm that promotes extensive inflammation in the lung, leading to many acute lung injuries, pulmonary edema, and eventually death. Mesenchymal stem cells (MSCs) might prove to be a treatment option as they have immunomodulation and regenerative properties. Clinical trials utilizing MSCs in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have provided a basis in treating post-COVID-19 patients. In this review, we discussed the effects of MSCs as an immunomodulator to reduce the severity and death in patients with COVID-19, including the usage of MSCs as an alternative regenerative therapy in post-COVID-19 patients. This review also includes the current clinical trials in utilizing MSCs and their potential future utilization for long-COVID treatments.
Acoustics have a wide range of uses, from noise-cancelling to ultrasonic imaging. There has been a surge in interest in developing acoustic-based approaches for biological and biomedical applications in the last decade. This review focused on the application of surface acoustic waves (SAW) based on interdigital transducers (IDT) for live-cell investigations, such as cell manipulation, cell separation, cell seeding, cell migration, cell characteristics, and cell behaviours. The approach is also known as acoustofluidic, because the SAW device is coupled with a microfluidic system that contains live cells. This article provides an overview of several forms of IDT of SAW devices on recently used cells. Conclusively, a brief viewpoint and overview of the future application of SAW techniques in live-cell investigations were presented.
Lentiviral vectors (LVs) play an important role in gene therapy and have proven successful in clinical trials. LVs are capable of integrating specific genetic materials into the target cells and allow for long-term expression of the cDNA of interest. The use of non-integrating LVs (NILVs) reduces insertional mutagenesis and the risk of malignant cell transformation over integrating lentiviral vectors. NILVs enable transient expression or sustained episomal expression, especially in non-dividing cells. Important modifications have been made to the basic human immunodeficiency virus (HIV) structures to improve the safety and efficacy of LVs. NILV-aided transient expression has led to more pre-clinical studies on primary immunodeficiencies, cytotoxic cancer therapies, and hemoglobinopathies. Recently, the third generation of self-inactivating LVs was applied in clinical trials for recombinant protein production, vaccines, gene therapy, cell imaging, and induced pluripotent stem cell (iPSC) generation. This review discusses the basic lentiviral biology and the four systems used for generating NILV designs. Mutations or modifications in LVs and their safety are addressed with reference to pre-clinical studies. The detailed application of NILVs in promising pre-clinical studies is also discussed.
Mechanotransduction is the process by which physical force is converted into a biochemical signal that is used in development and physiology; meanwhile, it is intended for the ability of cells to sense and respond to mechanical forces by activating intracellular signals transduction pathways and the relative phenotypic adaptation. It encompasses the role of mechanical stimuli for developmental, morphological characteristics, and biological processes in different organs; the response of cells to mechanically induced force is now also emerging as a major determinant of disease. Due to fluid shear stress caused by blood flowing tangentially across the lumen surface, cells of the cardiovascular system are typically exposed to a variety of mechanotransduction. In the body, tissues are continuously exposed to physical forces ranging from compression to strain, which is caused by fluid pressure and compressive forces. Only lately, though, has the importance of how forces shape stem cell differentiation into lineage-committed cells and how mechanical forces can cause or exacerbate disease besides organizing cells into tissues been acknowledged. Mesenchymal stem cells (MSCs) are potent mediators of cardiac repair which can secret a large array of soluble factors that have been shown to play a huge role in tissue repair. Differentiation of MSCs is required to regulate mechanical factors such as fluid shear stress, mechanical strain, and the rigidity of the extracellular matrix through various signaling pathways for their use in regenerative medicine. In the present review, we highlighted mechanical influences on the differentiation of MSCs and the general factors involved in MSCs differentiation. The purpose of this study is to demonstrate the progress that has been achieved in understanding how MSCs perceive and react to their mechanical environment, as well as to highlight areas where more research has been performed in previous studies to fill in the gaps.
The chimeric antigen receptor (CAR) plays a dynamic role in targeting tumour-associated antigens in cancer cells. This novel therapeutic discovery combines fragments of monoclonal antibodies with the signalling and co-stimulatory domains that have been modified to its current fourth generation. CAR has been widely implemented in T-cells and natural killer (NK) cells immunotherapy. The significant advancement in CAR technology is evident based on numerous ongoing clinical trials on CAR-T/-NK cells and successful CAR-related products such as Kymriah (Novartis) and Yescarta (Kite Pharma, Gilead). Another important cell-based therapy is the engineering of mesenchymal stem cells (MSC). Researchers have been exploring MSCs and their innate homing abilities to tumour sites and secretion cytokines that bridge both CAR and MSC technologies as a therapeutic agent. This combination allows for both therapies to overcome each one’s flaw as an immunotherapy intervention. Herein, we have provided a concise review on the background of CAR and its applications in different cancers, as well as MSCs’ unique ability as delivery vectors for cancer therapy and the possibility of enhancing the CAR-immune cells’ activity. Hence, we have highlighted throughout this review the synergistic effects of both interventions.
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