Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review.

Cancer is the second leading contributor to global deaths caused by non-communicable diseases. The cancer cells are known to interact with the surrounding non-cancerous cells, including the immune cells and stromal cells, within the tumor microenvironment (TME) to modulate the tumor progression, metastasis and resistance. Currently, chemotherapy and radiotherapy are the standard treatments for cancers. However, these treatments cause a significant number of side effects, as they damage both the cancer cells and the actively dividing normal cells indiscriminately. Hence, a new generation of immunotherapy using natural killer (NK) cells, cytotoxic CD8+ T-lymphocytes or macrophages was developed to achieve tumor-specific targeting and circumvent the adverse effects. However, the progression of cell-based immunotherapy is hindered by the combined action of TME and TD-EVs, which render the cancer cells less immunogenic. Recently, there has been an increase in interest in using immune cell derivatives to treat cancers. One of the highly potential immune cell derivatives is the NK cell-derived EVs (NK-EVs). As an acellular product, NK-EVs are resistant to the influence of TME and TD-EVs, and can be designed for "off-the-shelf" use. In this systematic review, we examine the safety and efficacy of NK-EVs to treat various cancers in vitro and in vivo.

Biodistribution of mesenchymal stem cells (MSCs) in animal models and implied role of exosomes following systemic delivery of MSCs: a systematic review.

Mesenchymal stem cells (MSC) are promising candidates to combat the growing rates of chronic degenerative diseases. These cells provide regeneration and/or differentiation into other cell types, and secrete various trophic factors that participate in migration, proliferation, and immunomodulation. However, the novelty of MSC research has noticeably declined as common barriers and unresolved challenges prevent further progress. A common issue is the low survivability and migration of systemically infused MSC towards targeted regions. Nevertheless, successful clinical treatment of various chronic diseases suggests that the MSCs may have an alternative mechanism. Recent advancements have shown labelling and imaging techniques to be a reliable source of data. These data not only illustrate the biodistribution but can be referenced to either support and/or improve the specificities of the cellular therapy construct. In this review, we compile recent studies between 2017 and 2021 to determine the homing and migration of MSCs by specific and peripherally-targeted organs. We also compare the different cell-tracking assays with the safety and efficacy of their therapeutic construct. We found that the common route of MSCs occurred in the lungs, liver, kidney and spleen. Furthermore, MSCs were also able to home and migrate towards targeted or injured organs such as the heart and lymph nodes. Although the MSCs were not detectable by the end of the study, the tested animals had significantly improved in terms of the disease symptoms and their related comorbidities. Thus, we hypothesize that the secretion of exosomes had contributed to this phenomenon.

Safety study of allogeneic mesenchymal stem cell therapy in animal model.

Intravenous (IV) infusion of mesenchymal stem cells (MSCs) from nascent tissues like Wharton's Jelly of the umbilical cord is reported to offer therapeutic effects against chronic diseases. However, toxicological data essential for the clinical application of these cells are limited. Thus, this study aimed to determine the safety of IV infusion of Wharton's Jelly derived MSCs (WJ-MSCs) in rats. Fifteen male Sprague-Dawley rats were randomised into the control or treatment group. Each group received an equal volume of saline or WJ-MSC (10 × 106 cell/kg) respectively. The animals were evaluated for physical, biochemical and haematological changes at Week 0, 2, 4, 8 and 12 during the 12-week study. Acute toxicity was performed during Week 2 and sub-chronic toxicity during Week 12. At the end of the study, the relative weight of organs was calculated and histology was performed for lung, liver, spleen and kidney. The findings from physical, serum biochemistry and complete blood count demonstrated no statistically significant differences between groups. However, pathological evaluation reported minor inflammation in the lungs for all groups, but visible healing and resolution of inflammation were observed in the treatment group only. Additionally, the histological images of the treatment group had significantly improved pulmonary structures compared to the control group. In summary, the IV administration of WJ-MSC was safe in the rats. Further studies are needed to determine the long-term safety of the WJ-MSC in both healthy and diseased animal models.

Stem cells as a potential therapy in managing various disorders of metabolic syndrome: a systematic review.

Recent explorations on mesenchymal stem/stromal cells (MSC) have reported a promising future for cell-based therapies. MSCs are widely sourced from various tissues and express unique properties of regenerative potential and immunomodulation. Currently, there is a growing interest in utilizing MSC for treatment of chronic diseases to overcome the drawbacks of chemical drugs. Metabolic Syndrome (MetS) is described as a cluster of metabolic abnormalities categorized as abdominal obesity, dyslipidaemia, hypertension, hypertriglyceridemia, and hyperglycaemia. Patients diagnosed with MetS have a high predisposition for developing cardiovascular complications, diabetes, non-alcoholic fatty liver diseases, bone loss, cancer, and mortality. Hence, research on MSC as therapy for MetS and related diseases, is greatly valued and are advantaged by the low immunogenicity with high regenerative capacity. However, there are many obstacles to be addressed such as the safety, efficacy, and consistency of different MSC sources. Additionally, factors such as effective dose level and delivery method are equally important to achieve uniform therapeutic outcomes. This systematic review discusses the potential roles of MSC in managing the multiple clusters of MetS. Research articles during the past 20 years were systematically searched and filtered to update the progress in the field of MSC therapy in managing various components of MetS. The different sources of MSC, dosage, method of delivery and outcome measures for the stem cell therapies were compiled from the systematically selected research articles. It can be concluded from the review of the selected articles that MSCs can improve the various disorders of MetS such as abdominal obesity, hyperglycaemia, hypertriglyceridemia and hypertension, and represent a promising alternative to conventional therapy of the MetS cluster.

Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review.

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling.