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

2D-Block Geminals: a non 1-orthogonal and non 0-seniority model with reduced computational complexity

We present a new geminal product wave function ansatz where the geminals are not constrained to be strongly orthogonal nor to be of seniority zero. Instead, we introduce weaker orthogonality constraints between geminals which significantly lower the computational effort, without sacrificing the indistinguishability of the electrons. That is to say, the electron pairs corresponding to the geminals are not fully distinguishable, and their product has still to be antisymmetrized according to the Pauli principle to form a \textit{bona fide} electronic wave function.Our geometrical constraints translate into simple equations involving the traces of products of our geminal matrices. In the simplest non-trivial model, a set of solutions is given by block-diagonal matrices where each block is of size 2x2 and consists of either a Pauli matrix or a normalized diagonal matrix, multiplied by a complex parameter to be optimized. With this simplified ansatz for geminals, the number of terms in the calculation of the matrix elements of quantum observables is considerably reduced. A proof of principle is reported and confirms that the ansatz is more accurate than strongly orthogonal geminal products while remaining computationally affordable

Delocalization effects in singlet fission: Comparing models with two and three interacting molecules

We present surface hopping simulations of singlet fission in 2,5-bis(fluorene-9-ylidene)-2,5-dihydrothiophene (ThBF). In particular, we performed simulations based on quantum mechanics/molecular mechanics (QM/MM) schemes in which either two or three ThBF molecules are inserted in the QM region and embedded in their MM crystal environment. Our aim was to investigate the changes in the photodynamics that are brought about by extending the delocalization of the excited states beyond the minimal model of a dimer. In the simulations based on the trimer model, compared to the dimer-based ones, we observed a faster time evolution of the state populations, with the largest differences associated with both the rise and decay times for the intermediate charge transfer states. Moreover, for the trimer, we predicted a singlet fission quantum yield of ∼204%, which is larger than both the one extracted for the dimer (∼179%) and the theoretical upper limit of 200% for the dimer-based model of singlet fission. Although our study cannot account for the effects of extending the delocalization beyond three molecules, our findings clearly indicate how and why the singlet fission dynamics can be affected

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