This work addresses a paradigm shift in nanomedicine, evolving from the traditional delivery model, focused on the passive transport of molecules, to a nanocommunication model. It argues that nanoscale systems are dynamic entities that actively encode, transmit, and modulate complex biological signals. Studies demonstrate that nanoparticles acquire a “biomolecular corona” in biological fluids, redefining their biological identity and directly modulating immune signaling pathways. In parallel, exosomes use their membrane proteome as a programmable molecular address code, capable of predicting the metastatic tropism of tumors toward specific organs. In pathological contexts, such as pulmonary, neurodegenerative diseases, and endometriosis, these nanoscale platforms reprogram cellular communication networks and influence systemic therapeutic responses. Nanomedicine is moving towards becoming a discipline of biological signal engineering. From a nanocommunication perspective, interactions at the nano-bio interface are not merely transfers of compounds, but dynamic, context-dependent informational flows. Physicochemical properties structure messages that recipient cells decode in a non-linear manner. Thus, therapeutic efficacy extends beyond cargo release, encompassing the ability to intervene and reconfigure pathological signaling networks actively.
The primary objectives of this review were to assess the rate of immune rejection associated with previously conducted xenogeneic mesenchymal stem cell (MSC) transplantations and to identify the animal species involved in these studies. Gene knockout strategies represent a highly promising approach for cross-species transplantation, particularly in humans. This is crucial because the human body naturally produces various antibodies that can trigger immune rejection, affecting not only cellular and tissue grafts but also decellularized scaffolds. The articular microenvironment has emerged as an ideal target for MSC transplantation due to its unique immunoprivileged characteristics, notably a low infiltration of polymorphonuclear leukocytes. Stem cells (SCs) are undifferentiated cells characterized by their self-renewal capacity and varying potentials to differentiate into distinct cell lineages. These intrinsic properties unlock a broad spectrum of therapeutic applications for SCs in both human and veterinary medicine. However, when cellular, tissue, or organ transplantation is performed in an allogeneic or xenogeneic setting, immune rejection remains a significant hurdle. This mechanism primarily involves human leukocyte antigen (HLA) molecules belonging to the major histocompatibility complex (MHC). SCs, in turn, are considered immunologically privileged due to their low baseline surface expression of MHC class II and HLA-DR molecules. Such features may provide a crucial advantage for the application of xenogeneic SCs in treating various pathologies. This study reviewed research outcomes regarding SCs and xenotransplantation by systematically searching the SciELO and PUBMED databases for articles published between 2003 and 2023, finding that in 80
To provide a comprehensive overview of key findings in research involving AD-MSCs and IONPs. Recent studies demonstrate the use of rabbits as a source for obtaining AD-MSCs, although human and murine sources remain the most commonly used. Regarding cell viability and IONP concentration, it is observed that high levels of IONPs can negatively impact the viability of AD-MSCs. Therefore, concentrations below 50 µg/mL are recommended. As for the influence of IONPs on cell proliferation and differentiation, the results are still divergent. However, most studies do not identify statistically significant differences in these parameters compared to controls. Adipose-derived mesenchymal stem cells (AD-MSCs) have changed the scientific and medical community’s perspective on adipose tissue, primarily due to their relative ease of isolation compared to cells from other sources, while maintaining similar biological characteristics. Nanoparticles (NPs) are nanometric structures with dimensions ranging up to 100 nm and, over the years, iron oxide nanoparticles (IONPs) have been extensively investigated in the biomedical field due to their unique ability to interact with and modulate cellular biological functions. Advances in biotechnology have expanded therapeutic applications of AD-MSCs, with their combination with IONPs emerging as a highly promising strategy. However, this interaction is still recent, and its precise effects on AD-MSCs remain poorly understood. Therefore, this systematic review aims to provide an overview of the current knowledge regarding the influence of IONPs on AD-MSCs. All selected studies utilized adipose tissue as the source of MSCs, predominantly of human and murine origin, and indicated that IONP concentrations equal to or below 50 µg/mL are preferable, as higher nanoparticle levels may negatively affect AD-MSC viability. In addition, the intracellular localization of IONPs has been predominantly observed within lysosomes, endosomes, the perinuclear region, and the cytoplasm. Although current findings suggest a promising interaction between IONPs and AD-MSCs, the available literature remains limited and, occasionally, presents discrepant results. This highlights the need for further investigations to better elucidate the biological effects and safety of this association, particularly concerning future in vivo applications.
This review examines the mechanisms of acquired resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). While genetic bypass mutations are well-understood, the focus here is on lineage plasticity—a non-genetic process where cancer cells evade treatment by altering their cellular identity. The review aims to synthesize how drug-tolerant persister (DTP) cells utilize epigenetic and transcriptomic reprogramming to survive initial therapy, ultimately leading to a phenotypic continuum that ranges from epithelial-mesenchymal transition (EMT) to full histological transformation (e.g., adenocarcinoma to small cell lung cancer). Advances in single-cell transcriptomics (ScRNA-seq) are decoding cancer cell evasion dynamics, revealing key insights: RNA velocity analysis quantifies resistance velocity, predicting future cell-state trajectories beyond static biopsies; master regulons SOX2, SNAI2, and ASCL1 drive cellular plasticity; and mapping trajectories during minimal residual disease (MRD) uncovers vulnerabilities before clinical relapse, enabling targeted interventions. Lineage plasticity is a prevalent but underrecognized hurdle in treating NSCLC. By leveraging computational tools like RNA velocity and GRN inference, clinicians can better predict therapeutic escape routes. This framework supports a shift toward personalized medicine where early interventions, such as combining TKIs with epigenetic modifiers, target master regulators to disrupt plasticity. Such strategies may prevent histological transformation, optimize the timing of clinical trials, and ultimately reduce the risk of recurrence.
Localized cutaneous leishmaniasis (LCL) is the most prevalent form of leishmaniasis, with infection control primarily dependent on cell-mediated immunity. Lesion healing results from a complex interplay among immune cells and soluble mediators. Using Luminex technology, we evaluated circulating and lesion microenvironment immune mediators, including chemokines, cytokines, and growth factors, in patients with LCL and nonspecific dermatitis. A robust proinflammatory response was observed in the lesion microenvironment of LCL patients, characterized by elevated levels of growth factors, important immune mediators potentially involved in tissue repair. Predictive modeling identified FGF, G-CSF, GM-CSF, IL-2, and IL-9 as key immune mediators distinguishing LCL from nonspecific dermatitis. Our results reveal that LCL presents a distinct soluble immune mediator signature from nonspecific dermatitis, exhibiting a set of biomarkers that not only define its immune mediator signature but also signal a possible role in the tissue repair process. Furthermore, we characterized the profile of soluble immune mediators of LCL patients, categorized according to the time evolution lesion. Our analysis revealed a predominance of biomarkers within the lesion microenvironment in patients with recent lesions (< 2 months of evolution). On the other hand, in late lesions patients (> 2 months of evolution), our data showed a predominance of biomarkers in the systemic circulation. Collectively, these findings provide novel insights into the immunopathogenesis of LCL and highlight candidate immune mediators for targeted prognostic evaluation.
