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.

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.

The 14‐3‐3 family of proteins are highly conserved acidic eukaryotic proteins (25–32 kDa) abundantly present in the body. Through numerous binding partners, the 14‐3‐3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14‐3‐3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14‐3‐3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID‐19 has been linked to the 14‐3‐3 proteins by the interference of the SARS‐CoV‐2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14‐3‐3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14‐3‐3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14‐3‐3 proteins in the associated diseases was discussed.

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.

Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes. EVs are described as a membrane-enclosed cargo of functional biomolecules not limited to lipids, nucleic acid, and proteins. Interestingly, studies have correlated the biological role of MSC-EVs to the paracrine activity of MSCs. This key evidence has led to rigorous studies on MSC-EVs as an acellular alternative. Using EVs as a therapy was proposed as a model leading to improvements through increased safety; enhanced bioavailability due to size and permeability; reduced heterogeneity by selective and quantifiable properties; and prolonged shelf-life via long-term freezing or lyophilization. Yet, the identity and potency of EVs are still relatively unknown due to various methods of preparation and to qualify the final product. This is reflected by the absence of regulatory strategies overseeing manufacturing, quality control, clinical implementation, and product registration. In this review, the authors review the various production processes and the proteomic profile of MSC-EVs.

Regenerative medicine represents a paradigm shift in healthcare, aiming to restore tissue and organ function through innovative therapeutic strategies. Among these, bioprinting and extracellular vesicles (EVs) have emerged as promising techniques for tissue rejuvenation. EVs are small lipid membrane particles secreted by cells, known for their role as potent mediators of intercellular communication through the exchange of proteins, genetic material, and other biological components. The integration of 3D bioprinting technology with EVs offers a novel approach to tissue engineering, enabling the precise deposition of EV-loaded bioinks to construct complex three-dimensional (3D) tissue architectures. Unlike traditional cell-based approaches, bioprinted EVs eliminate the need for live cells, thereby mitigating regulatory and financial obstacles associated with cell therapy. By leveraging the synergistic effects of EVs and bioprinting, researchers aim to enhance the therapeutic outcomes of skin regeneration while addressing current limitations in conventional treatments. This review explores the evolving landscape of bioprinted EVs as a transformative approach for skin regeneration. Furthermore, it discusses the challenges and future directions in harnessing this innovative therapy for clinical applications, emphasizing the need for interdisciplinary collaboration and continued scientific inquiry to unlock its full therapeutic potential.