Stem cell tracking with nanoparticles for regenerative medicine purposes: An overview

Accurate and noninvasive stem cell tracking is one of the most important needs in regenerative medicine to determine both stem cell destinations and final differentiation fates, thus allowing a more detailed picture of the mechanisms involved in these therapies. Given the great importance and advances in the field of nanotechnology for stem cell imaging, currently, several nanoparticles have become standardized products and have been undergoing fast commercialization. This review has been intended to summarize the current use of different engineered nanoparticles in stem cell tracking for regenerative medicine purposes, in particular by detailing their main features and exploring their biosafety aspects, the first step for clinical application. Moreover, this review has summarized the advantages and applications of stem cell tracking with nanoparticles in experimental and preclinical studies and investigated present limitations for their employment in the clinical setting

Surgery after Neoadjuvant Chemotherapy: A Clip-Based Technique to Improve Surgical Outcomes, a Single-Center Experience

SIMPLE SUMMARY: Neoadjuvant chemotherapy (NACT) has an important role in the treatment of locally advanced breast cancer. After NACT, some lesions may be no longer visible at preoperative imaging, making breast and axillary conservative surgery more difficult. Among others, radiopaque clips are the most commonly used method to mark lymph nodes and tumor sites to tailor surgery in the post neoadjuvant setting. ABSTRACT: Background: This study aims to describe the surgical management of breast cancer patients after neoadjuvant chemotherapy, with attention to the impact on surgical outcomes of a clip-based marking technique. Methods: Patients who underwent NACT at the Breast Unit of the A. O Ordine Mauriziano of Turin from January 2018 and had a surgical intervention by January 2022 were included. Data on the feasibility of clip insertion, after-treatment visibility, and successful removal during surgery were collected prospectively. Surgical outcomes in terms of breast-conserving surgery and axillary dissection reduction were described. Results: In 51 patients who had surgery after NACT, 55 clips were placed (34 breast and 21 axillary clips). Ultrasound visibility of the clips was optimal (91%) as well as preoperative localization and retrieval within the surgical specimen. Moreover, the use of the clip positively affected surgical outcomes. In our study, clip insertion allowed to avoid mastectomy and axillary dissection in patients with a complete radiological response. Conclusions: In our findings, the use of breast and/or lymph node clips has proved to be a simple and effective method to improve surgical conservative management of breast cancer patients after NACT

Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) are adult multipotent stem cells located in various tissues, including the bone marrow. In contrast to terminally differentiated somatic cells, adult stem cells must persist and function throughout life to ensure tissue homeostasis and repair. For this reason, they must be equipped with DNA damage responses able to maintain genomic integrity while ensuring their lifelong persistence. Evaluation of hMSC response to genotoxic insults is of great interest considering both their therapeutic potential and their physiological functions. This study aimed to investigate the response of human bone marrow MSCs to the genotoxic agent Actinomycin D (ActD), a well-known anti-tumour drug. We report that hMSCs react by undergoing premature senescence driven by a persistent DNA damage response activation, as hallmarked by inhibition of DNA synthesis, p21 and p16 protein expression, marked Senescent Associated β-galactosidase activity and enlarged γH2AX foci co-localizing with 53BP1 protein. Senescent hMSCs overexpress several senescence-associated secretory phenotype (SASP) genes and promote motility of lung tumour and osteosarcoma cell lines in vitro. Our findings disclose a multifaceted consequence of ActD treatment on hMSCs that on the one hand helps to preserve this stem cell pool and prevents damaged cells from undergoing neoplastic transformation, and on the other hand alters their functional effects on the surrounding tissue microenvironment in a way that might worsen their tumour-promoting behaviour

Human mesenchymal stem cells labelled with dye-loaded amorphous silica nanoparticles: long-term biosafety, stemness preservation and traceability in the beating heart

Treatment of myocardial infarction with mesenchymal stem cells (MSCs) has proven beneficial effects in both animal and clinical studies. Engineered silica nanoparticles (SiO2-NPs) have been extensively used as contrast agents in regenerative medicine, due to their resistance to degradation and ease of functionalization. However, there are still controversies on their effective biosafety on cellular systems. In this perspective, the aims of the present study are: 1) to deeply investigate the impact of amorphous 50 nm SiO2-NPs on viability and function of human bone marrow-derived MSCs (hMSCs); 2) to optimize a protocol of harmless hMSCs labelling and test its feasibility in a beating heart model. Optimal cell labelling is obtained after 16 h exposure of hMSCs to fluorescent 50 nm SiO2-NPs (50 µg mL(-1)); interestingly, lysosomal activation consequent to NPs storage is not associated to oxidative stress. During prolonged culture hMSCs do not undergo cyto- or genotoxicity, preserve their proliferative potential and their stemness/differentiation properties. Finally, the bright fluorescence emitted by internalized SiO2-NPs allows both clear visualization of hMSCs in normal and infarcted rat hearts and ultrastructural analysis of cell engraftment inside myocardial tissue. Overall, 50 nm SiO2-NPs display elevated compatibility with hMSCs in terms of lack of cyto- and genotoxicity and maintenance of important features of these cells. The demonstrated biosafety, combined with proper cell labelling and visualization in histological sections, make these SiO2-NPs optimal candidates for the purpose of stem cell tracking inside heart tissue

Risk Assessment and Risk Minimization in Nanomedicine: A Need for Predictive, Alternative, and 3Rs Strategies

The use of nanomaterials in medicine has grown very rapidly, leading to a concern about possible health risks. Surely, the application of nanotechnology in medicine has many significant potentialities as it can improve human health in at least three different ways: by contributing to early disease diagnosis, improved treatment outcomes and containment of health care costs. However, toxicology or safety assessment is an integral part of any new medical technology and the nanotechnologies are no exception. The principle aim of nanosafety studies in this frame is to enable safer design of nanomedicines. The most urgent need is finding and validating novel approaches able to extrapolate acute in vitro results for the prediction of chronic in vivo effects and to this purpose a few European initiatives have been launched. While a “safe-by-design” process may be considered as utopic, “safer-by-design” is probably a reachable goal in the field of nanomedicine