President's letter on unproven cellular therapy

The International Society for CellularTherapy (ISCT; www.celltherapysociety.org), with a strategy adopted more than 5 year ago (Gunter KC et al. Cytotherapy 2010), wishes to continue raising awareness about unproven cellular therapies. All over the world, there is a legitimate effort to introduce cellular therapies into the clinic; however, at the same time a large number of clinics have begun offering cell-based intervention for a variety of diseases with questionable safety or efficacy data or an unclear scientific rationale.This has led to many vulnerable patients subjecting themselves to unproven cellular therapies with no adequate regulatory oversight or reliable information about risks or benefit. For this reason, ISCT feels the need to provide a new source of information: an open document that represents a sharing of knowledge by leaders in the field

The survey of the Basilica di Collemaggio in L’Aquila with a system of terrestrial imaging and most proven techniques

The proposed job concerns the evaluation of a series of surveys carried out in the context of a campaign of studies begun in 2015 with the objective of comparing the accuracies obtainable with the systems of terrestrial imaging, compared to unmanned aerial vehicle imaging and laser scanner survey. In particular, the authors want to test the applicability of a system of imaging rover (IR), an innovative terrestrial imaging system, that consists of a multi-camera with integrated global positioning system (GPS)/global navigation satellite system (GNSS) receiver, that is very recently released technique, and only a few literature references exist on the specific subject. In detail, the IR consists of a total of 12 calibrated cameras – seven “panorama” and five downward-looking – providing complete site documentation that can potentially be used to make photogrammetric measurements. The data acquired in this experimentation were then elaborated with various software packages in order to obtain point clouds and a three-dimensional model in different cases, and a comparison of the various results obtained was carried out. Following, the case study of the Basilica di Santa Maria di Collemaggio in L’Aquila is reported; Collemaggio is an UNESCO world heritage site; it was damaged during the seismic event of 2009, and its restoration is still in progress

A brief history of Florentine physics from the 1920s to the end of the 1960s

The history of the Institute of Physics at the University of Florence is traced from the beginning of the 20th century, with the arrival of Antonio Garbasso as Director (1913), to the 1960s. Thanks to Garbasso's expertise, not only did the Institute gain new premises on Arcetri hill, where the Astronomical Observatory was already located, but it also formed a brilliant group of young physicists made up of Rita Brunetti, Enrico Fermi, Franco Rasetti, Enrico Persico, Bruno Rossi, Gilberto Bernardini, Daria Bocciarelli, Giuseppe Occhialini and Giulio Racah, who were engaged in the emerging fields of Quantum Mechanics and Cosmic Rays. This {\it Arcetri School} disintegrated in the late 1930s not only for the transfer of its protagonists to chairs in other universities but also for the racial laws and the environment created by the fascist regime. After the war, the legacy was taken up by some students of this school who formed research groups in the field of nuclear physics and elementary particle physics. As far as theoretical physics was concerned, after the Fermi and Persico periods these studies enjoyed a new expansion towards the end of the 1950s, with the arrival of Giacomo Morpurgo and above all, that of Raoul Gatto, who created the first real Italian school of Theoretical Physics at Arcetri.Comment: Latex file, 11 figure

Response to Nature commentary “Clear up this stem-cell mess”

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Cell therapies for pancreatic beta-cell replenishment.

The current treatment approach for type 1 diabetes is based on daily insulin injections, combined with blood glucose monitoring. However, administration of exogenous insulin fails to mimic the physiological activity of the islet, therefore diabetes often progresses with the development of serious complications such as kidney failure, retinopathy and vascular disease. Whole pancreas transplantation is associated with risks of major invasive surgery along with side effects of immunosuppressive therapy to avoid organ rejection. Replacement of pancreatic beta-cells would represent an ideal treatment that could overcome the above mentioned therapeutic hurdles. In this context, transplantation of islets of Langerhans is considered a less invasive procedure although long-term outcomes showed that only 10 % of the patients remained insulin independent five years after the transplant. Moreover, due to shortage of organs and the inability of islet to be expanded ex vivo, this therapy can be offered to a very limited number of patients. Over the past decade, cellular therapies have emerged as the new frontier of treatment of several diseases. Furthermore the advent of stem cells as renewable source of cell-substitutes to replenish the beta cell population, has blurred the hype on islet transplantation. Breakthrough cellular approaches aim to generate stem-cell-derived insulin producing cells, which could make diabetes cellular therapy available to millions. However, to date, stem cell therapy for diabetes is still in its early experimental stages. This review describes the most reliable sources of stem cells that have been developed to produce insulin and their most relevant experimental applications for the cure of diabetes

Dynamic cultivation of mesenchymal stem cell aggregates

Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions\u2014such as hypoxia, three-dimensional environments, and dynamic cultivation\u2014prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates

In vitro testing for genotoxicity of indigo naturalis assessed by micronucleus test.

In the field of cosmetic dyes, used for coloring the hair and skin, there is a clear tendency to replace the widely used synthetic dyes by natural colorants, such as henna and mixtures of henna with indigo. The aim of this study was to estimate the genotoxicity of water and DMSO solutions of indigo naturalis (prepared from Indigofera tinctoria leaves) using the cytokinesis-blocked micronucleus (CBMN) assay in the human metabolically active HepG2 cell line. The cytotoxic effects of indigo solutions were first assessed by propidium iodide and fluorescein-diacetate simultaneous staining. For both solutions, cytotoxicity was always under 10%. Data obtained in the CBMN assay (for all concentrations tested) indicated that the frequency of MN (micronuclei) in exposed cells was no higher than the control. Both the water and DMSO solutions showed the same behavior. These results indicate that indigo naturalis exhibits neither cytotoxicity, nor genotoxicity for all concentrations tested, which may justify excluding indigofera and its components from the list of carcinogenic agents

Rare breast cancer subtypes: Histological, molecular, and clinical peculiarities

Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies. \ua9 AlphaMed Press

Mineralization by mesenchymal stromal cells is variously modulated depending on commercial platelet lysate preparations

Background aims: Numerous cellular models have been developed to investigate calcification for regenerative medicine applications and for the identification of therapeutic targets in various complications associated with age-related diseases. However, results have often been contradictory due to specific culture conditions, cell type ontogeny and aging status. Human platelet lysate (hPL) has been recently investigated as valuable alternative to fetal bovine serum (FBS) in cell culture and bone regeneration. A parallel comparison of how all these multiple factors may converge to influence mineralization has yet to be reported. Methods: To compare mineralization of human mesenchymal cell types known to differ in extracellular matrix calcification potency, bone marrowâderived mesenchymal stromal cells and dermal fibroblasts from neonatal and adult donors, at both low and high passages, were investigated in an ex vivo experimental model by supplementing the osteogenic induction medium with FBS or with hPL. Four commercial hPL preparations were profiled by liquid chromatography/electrospray ionization quadrupole time-of-flight spectrometry, and mineralization was visualized by von Kossa staining and quantified by morphometric evaluations after 9, 14 and 21 days of culture. Results: Data demonstrate that (i) commercial hPL preparations differ according to mass spectra profiles, (ii) hPL variously influences mineral deposition depending on cell line and possibly on platelet product preparation methods, (iii) donor age modifies mineral deposition in the presence of the same hPL and (iv) reduced in vitro proliferative capacity affects osteogenic induction and response to hPL. Conclusion: Despite the standardized procedures applied to obtain commercial hPL, this study highlights the divergent effects of different preparations and emphasizes the importance of cellular ontology, donor age and cell proliferative capacity to optimize the osteogenic induction capabilities of mesenchymal stromal cells and design more effective cell-based therapeutic protocols