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Abstract In recent decades, human mesenchymal stem cells (hMSCs) have gained momentum in the field of cell therapy for treating cartilage and bone injuries. Despite the tri-lineage multipotency, proliferative properties, and potent immunomodulatory effects of hMSCs, their clinical potential is hindered by donor variations, limiting their use in medical settings. To address this challenge, gene delivery technologies have emerged as a promising approach to modulate the phenotype and commitment of hMSCs towards specific cell lineages, thereby enhancing osteochondral repair strategies. This review provides a comprehensive overview of current non-viral gene delivery approaches used to engineer MSCs, highlighting key factors such as the choice of nucleic acid or delivery vector, transfection strategies, and experimental parameters. Additionally, it outlines various protocols and methods for qualitative and quantitative evaluation of their therapeutic potential as a delivery system in osteochondral regenerative applications. In summary, this technical review offers a practical guide for optimizing non-viral systems in osteochondral regenerative approaches. Graphical Abstract hMSCs constitute a key target population for gene therapy techniques. Nevertheless, there is a long way to go for their translation into clinical treatments. In this review, we remind the most relevant transfection conditions to be optimized, such as the type of nucleic acid or delivery vector, the transfection strategy, and the experimental parameters to accurately evaluate a delivery system. This survey provides a practical guide to optimizing non-viral systems for osteochondral regenerative approaches.

Senescence is a process characterized by a prolonged irreversible cell-cycle arrest. The accumulation of senescent cells in tissues is related to aging and to the development of age-related diseases. Recently, gene therapy has emerged as a powerful tool for treating age-associated diseases by the transference of specific genes into the target cell population. However, the high sensitivity of senescent cells significantly precludes their genetic modification via classical viral and non-viral systems. Niosomes are self-assembled non-viral nanocarriers that exhibit important advantages due to their elevated cytocompatibility, versatility, and cost-efficiency, arising as a new alternative for genetic modification of senescent cells. In this work, we explore for the first time the use of niosomes for genetic modification of senescent umbilical cord-derived mesenchymal stem cells. We report that niosome composition greatly affected transfection efficiency; those formulations prepared in medium with sucrose and containing cholesterol as helper lipid being the most suitable to transfect senescent cells. Moreover, resulting niosome formulations exhibited a superior transfection efficiency with a markedly less cytotoxicity than the commercial reagent Lipofectamine. These findings highlight the potentiality of niosomes as effective vectors for genetic modification of senescent cells, providing new tools for the prevention and/or treatment of age-related diseases.

Abstract Introduction We present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas. Case presentation We extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67. Conclusion These findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique.

Abstract Introduction Oncocytic carcinoma is a rare proliferation of cytomorphologically malignant oncocytes mainly found in glandular tissue, accounting for 0.5% of all epithelial salivary gland malignancies and 0.18% of all epithelial salivary gland tumors. Case presentation We report a case of oncocytic carcinoma arising in the parotid gland of a 65-year-old Caucasian man. Our patient initially underwent left superficial parotidectomy, including the removal of the mass. A close follow-up was made, and four years after first surgery cervical lymph node metastases were confirmed. Therefore, a complete parotidectomy and radical neck dissections were performed. There were no complications and no sign of recurrence after six months of follow-up. Conclusion Oncocytic carcinoma is an extremely rare malignancy in the salivary glands. Prophylactic neck dissection may be indicated for tumors larger than 2 cm in diameter (our patient's tumor was 2.5 cm at its greatest diameter). The clinical course of our patient, with the appearance of cervical lymph node metastases after four years of follow-up, supports this approach. Further investigation of the prognosis and correct treatment of patients with oncocytic carcinoma are required as more cases are reported.