[Ethical approach to the issue of confinement of the elderly in the context of the COVID-19 pandemic: Prevention of frailty versus risk of vulnerability]. / Une approche éthique de la question du confinement des personnes âgées en contexte de pandémie COVID-19 : la prévention des fragilités face au risque de vulnérabilité.

COVID-19 pandemic particularly affects older people and exposes them to a higher risk of mortality. Containment, social distancing and isolation measures have been implemented to limit viral transmission. While there is a clear rationale for reducing the contagiousness of the infection through this means, the adverse consequences of this social isolation, especially for this heterogeneous, aged and frail people, are difficult to apprehend. In particular, the disruption of the usual support and care ecosystems at home or in institutions may paradoxically increase the frailty of these people and lead to adverse events we wanted to avoid. On the other hand, the risk of a decrease in the older person's empowerment regarding his or her own health and social life decisions requires particular vigilance to prevent the risk of societal ageism. Regarding this population in particular, a possible conflict of values between individual and collective protection on one hand and respect for autonomy and independence on the other hand could exist. This article proposes an ethical reflection on the issue of containment of frail ageing people, based on medical ethics principles, in order to open up positive approaches of vulnerability that guarantee respect for the dignity of the person and equity in care access.

Analysis of resorbable mesh implants in short-term human muscular fascia cultures: a pilot study.

PURPOSE: Alteration in fascial tissue collagen composition represents a key factor in hernia etiology and recurrence. Both resorbable and non-resorbable meshes for hernia repair are currently used in the surgical setting. However, no study has investigated so far the role of different implant materials on collagen deposition and tissue remodeling in human fascia. The aim of the present study was to develop a novel ex vivo model of human soft tissue repair mesh implant, and to test its suitability to investigate the effects of different materials on tissue remodeling and collagen composition. METHODS: Resorbable poly-4-hydroxybutyrate and non-resorbable polypropylene mesh implants were embedded in human abdominal fascia samples, mimicking common surgical procedures. Calcein-AM/Propidium Iodide vital staining was used to assess tissue vitality. Tissue morphology was evaluated using Mallory trichrome and hematoxylin and eosin staining. Collagen type I and III expression was determined through immunostaining semi-quantification by color deconvolution. All analyses were performed after 54 days of culture. RESULTS: The established ex vivo model showed good viability at 54 days of culture, confirming both culture method feasibility and implants biocompatibility. Both mesh implants induced a disorganization of collagen fibers pattern. A statistically significantly higher collagen I/III ratio was detected in fascial tissue samples cultured with resorbable implants compared to either non-resorbable implants or meshes-free controls. CONCLUSION: We developed a novel ex vivo model and provided evidence that resorbable polyhydroxybutyrate meshes display better biomechanical properties suitable for proper restoration in surgical hernia repair.

Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study.

INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.

Synchrotron Radiation Applied to Real-Time Studies of the Kinetics of Growth of Aluminum Nitride Thin Multilayers.

This article reports the design, construction, and first use of an experimental device consisting of a specially designed vacuum chamber equipped with a reactive sputtering magnetron (RSM) to be used for controlled deposition of thin films on a Si(100) flat substrate. The setup was designed to allow for in situ and real-time recordings of X-ray diffraction patterns during the growth of the deposited films and was installed in the X-ray diffraction and spectroscopy beamline emerging from a superconducting wiggler source at the Brazilian Synchrotron Light Laboratory. The first use of the RSM setup was an in situ and real-time X-ray diffraction study of processes of growth of multilayered aluminum nitride thin films, whereas the operation parameters of the reactor were sequentially changed. This sequential process led to the development of multilayered films. Alternate variations in chamber pressure and magnetron power density allowed us to obtain thin films composed of several micrometer thick layers, with alternate amorphous and (10·0), (00·2), or (10·1) textured polycrystalline structures.

A finite element analysis of diaphragmatic hernia repair on an animal model.

The diaphragm is a mammalian skeletal muscle that plays a fundamental role in the process of respiration. Alteration of its mechanical properties due to a diaphragmatic hernia contributes towards compromising its respiratory functions, leading to the need for surgical intervention to restore the physiological conditions by means of implants. This study aims to assess via numerical modeling biomechanical differences between a diaphragm in healthy conditions and a herniated diaphragm surgically repaired with a polymeric implant, in a mouse model. Finite Element models of healthy and repaired diaphragms are developed from diagnostic images and anatomical samples. The mechanical response of the diaphragmatic tendon is described by assuming an isotropic hyperelastic model. A similar constitutive model is used to define the mechanical behavior of the polymeric implant, while the muscular tissue is modeled by means of a three-element Hill's model, specifically adapted to mouse muscle fibers. The Finite Element Analysis is addressed to simulate diaphragmatic contraction in the eupnea condition, allowing the evaluation of diaphragm deformation in healthy and herniated-repaired conditions. The polymeric implant reduces diaphragm excursion compared to healthy conditions. This explains the possible alteration in the mechanical functionality of the repaired diaphragm. Looking to the surgical treatment of diaphragmatic hernia in human neonatal subjects, this study suggests the implementation of alternative approaches based on the use of biological implants.

Synthesis and chemical characterization of several perfluorinated sialic acid glycals and evaluation of their in vitro antiviral activity against Newcastle disease virus.

Newcastle Disease Virus (NDV), belonging to the Paramyxoviridae family, causes a serious infectious disease in birds, resulting in severe losses in the poultry industry every year. Haemagglutinin neuraminidase glycoprotein (HN) has been recognized as a key protein in the viral infection mechanism, and its inhibition represents an attractive target for the development of new drugs based on sialic acid glycals, with the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid (Neu5Ac2en) as their backbone. Herein we report the synthesis of several Neu5Ac2en glycals and of their perfluorinated C-5 modified derivatives, including their respective stereoisomers at C-4, together with evaluation of their in vitro antiviral activity. While all synthesized compounds were found to be active HN inhibitors in the micromolar range, we found that their potency was influenced by the chain-length of the C-5 perfluorinated acetamido functionality. Thus, the binding modes of the inhibitors were also investigated by performing a docking study. Moreover, the perfluorinated glycals were found to be more active than the corresponding normal C-5 acylic derivatives. Finally, cell-cell fusion assays on NDV infected cells revealed that the addition of a newly synthesized C-4α heptafluorobutyryl derivative almost completely inhibited NDV-induced syncytium formation.

Diffusion MRI for rectal cancer staging: ADC measurements before and after ultrasonographic gel lumen distension.

OBJECTIVES: To compare Apparent Diffusion Coefficient (ADC) measurements in rectal neoplastic lesions before and after lumen distension obtained with sonography transmission gel. METHODS: From January 2014 to July 2016, 25 patients (average age 63.7, range 41-85, 18 males) were studied for pre-treatment rectal cancer staging using a 1.5T MRI. Diffusion MRI was obtained using echo-planar imaging with b=800 value; all patients were studied acquiring diffusion sequences with and without rectal lumen distension obtained using sonography transmission gel. In both diffusion sequences, two blinded readers calculated border ADC values and small ADC values, drawing regions of interest respectively along tumour borders and far from tumour borders. Mean ADC values among readers - for each type of ADC measurement - were compared using Wilcoxon matched pairs signed rank test. Correlation was assessed using Pearson analysis. RESULTS: Border ADC mean value for diffusion MR sequences without endorectal contrast was 1.122mm2/sec, with 95% Confidence Interval (CI)=1.02-1.22; using gel lumen distension, higher border ADC mean value of 1.269mm2/s (95% CI=1.16-1.38) was obtained. Wilcoxon matched pairs signed rank test revealed statistical difference (p<0.01); a strong Pearson correlation was reported, with r value of 0.69. Small-ADC mean value was 1.038mm2/s (95% CI=0.91-1.16) for diffusion sequences acquired without endorectal distension and 1.127mm2/s (95% CI=0.98-1.27) for diffusion sequences obtained after endorectal gel lumen distension. Wilcoxon analysis did not show statistical difference (p=0.13). A very strong positive correlation was observed, with r value of 0.81. CONCLUSIONS: ADC measurements are slightly higher using endorectal sonographic transmission gel; ROI should be traced far from tumour borders, to minimize gel filled-pixel along the interface between lumen and lesion. Further studies are needed to investigate better reliability of ADC in rectal cancer MRI using sonographic gel intraluminal distension.

First steps to define murine amniotic fluid stem cell microenvironment.

Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit+ cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit+ cells present both in the amniotic fluid and in the amnion. Secondly, to analyze the AFS cell microenvironment, we injected murine YFP+ embryonic stem cells (ESC) into the amniotic fluid of E13.5 wild type embryos. Four days after transplantation we found that YFP+ sorted cells maintained the expression of pluripotency markers and that ESC adherent to the amnion were more similar to original ESC in respect to those isolated from the amniotic fluid. Moreover, cytokines evaluation and oxygen concentration analysis revealed in this microenvironment the presence of factors that are considered key regulators in stem cell niches. This is the first indication that AFS cells reside in a microenvironment that possess specific characteristics able to maintain stemness of resident and exogenous stem cells.

Improvement of diaphragmatic performance through orthotopic application of decellularized extracellular matrix patch.

Muscle tissue engineering can provide support to large congenital skeletal muscle defects using scaffolds able to allow cell migration, proliferation and differentiation. Acellular extracellular matrix (ECM) scaffold can generate a positive inflammatory response through the activation of anti-inflammatory T-cell populations and M2 polarized macrophages that together lead to a local pro-regenerative environment. This immunoregulatory effect is maintained when acellular matrices are transplanted in a xenogeneic setting, but it remains unclear whether it can be therapeutic in a model of muscle diseases. We demonstrated here for the first time that orthotopic transplantation of a decellularized diaphragmatic muscle from wild animals promoted tissue functional recovery in an established atrophic mouse model. In particular, ECM supported a local immunoresponse activating a pro-regenerative environment and stimulating host muscle progenitor cell activation and migration. These results indicate that acellular scaffolds may represent a suitable regenerative medicine option for improving performance of diseased muscles.

Laparoscopic ventral/incisional hernia repair: updated Consensus Development Conference based guidelines

BACKGROUND: The Executive board of the Italian Society for Endoscopic Surgery (SICE) promoted an update of the first evidence-based Italian Consensus Conference Guidelines 2010 because a large amount of literature has been published in the last 4 years about the topics examined and new relevant issues. METHODS: The scientific committee selected the topics to be addressed: indications to surgical treatment including special conditions (obesity, cirrhosis, diastasis recti abdominis, acute presentation); safety and outcome of intraperitoneal meshes (synthetic and biologic); fixing devices (absorbable/non-absorbable); abdominal border and parastomal hernia; intraoperative and perioperative complications; and recurrent ventral/incisional hernia. All the recommendations are the result of a careful and complete literature review examined with autonomous judgment by the entire panel. The process was supervised by experts in methodology and epidemiology from the most qualified Italian institution. Two external reviewers were designed by the EAES and EHS to guarantee the most objective, transparent, and reliable work. The Oxford hierarchy (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence") was used by the panel to grade clinical outcomes according to levels of evidence. The recommendations were based on the grading system suggested by the GRADE working group. RESULTS AND CONCLUSIONS: The availability of recent level 1 evidence (a meta-analysis of 10 RCTs) allowed to recommend that not only laparoscopic repair is an acceptable alternative to the open repair, but also it is advantageous in terms of shorter hospital stay and wound infection rate. This conclusion appears to be extremely relevant in a clinical setting. Indications about specific conditions could also be issued: laparoscopy is recommended for the treatment of recurrent ventral hernias and obese patients, while it is a potential option for compensated cirrhotic and childbearing-age female patients. Many relevant and controversial topics were thoroughly examined by this consensus conference for the first time. Among them are the issue of safety of the intraperitoneal mesh placement, traditionally considered a major drawback of the laparoscopic technique, the role for the biologic meshes, and various aspects of the laparoscopic approach for particular locations of the defect such as the abdominal border or parastomal hernias.(AU)

Genomic prediction for tick resistance in Braford and Hereford cattle.

One of the main animal health problems in tropical and subtropical cattle production is the bovine tick, which causes decreased performance, hide devaluation, increased production costs with acaricide treatments, and transmission of infectious diseases. This study investigated the utility of genomic prediction as a tool to select Braford (BO) and Hereford (HH) cattle resistant to ticks. The accuracy and bias of different methods for direct and blended genomic prediction was assessed using 10,673 tick counts obtained from 3,435 BO and 928 HH cattle belonging to the Delta G Connection breeding program. A subset of 2,803 BO and 652 HH samples were genotyped and 41,045 markers remained after quality control. Log transformed records were adjusted by a pedigree repeatability model to estimate variance components, genetic parameters, and breeding values (EBV) and subsequently used to obtain deregressed EBV. Estimated heritability and repeatability for tick counts were 0.19 ± 0.03 and 0.29 ± 0.01, respectively. Data were split into 5 subsets using k-means and random clustering for cross-validation of genomic predictions. Depending on the method, direct genomic value (DGV) prediction accuracies ranged from 0.35 with Bayes least absolute shrinkage and selection operator (LASSO) to 0.39 with BayesB for k-means clustering and between 0.42 with BayesLASSO and 0.45 with BayesC for random clustering. All genomic methods were superior to pedigree BLUP (PBLUP) accuracies of 0.26 for k-means and 0.29 for random groups, with highest accuracy gains obtained with BayesB (39%) for k-means and BayesC (55%) for random groups. Blending of historical phenotypic and pedigree information by different methods further increased DGV accuracies by values between 0.03 and 0.05 for direct prediction methods. However, highest accuracy was observed with single-step genomic BLUP with values of 0.48 for -means and 0.56, which represent, respectively, 84 and 93% improvement over PBLUP. Observed random clustering cross-validation breed-specific accuracies ranged between 0.29 and 0.36 for HH and between 0.55 and 0.61 for BO, depending on the blending method. These moderately high values for BO demonstrate that genomic predictions could be used as a practical tool to improve genetic resistance to ticks and in the development of resistant lines of this breed. For HH, accuracies are still in the low to moderate side and this breed training population needs to be increased before genomic selection could be reliably applied to improve tick resistance.

Intrapartum fetal heart rate monitoring interpretation in labour: a critical appraisal.

Electronic fetal monitoring (EFM) has been introduced in the obstetrics practice as a test to identify the first signs of fetal deterioration, allowing a prompt intervention to reduce neonatal morbidity and mortality. However, results from clinical trials fail to demonstrate a clear benefit with the use of EFM. No decrease in the incidence of cerebral palsy due to intrapartum asphyxia has been achieved and a significant increase in the rate of operative deliveries and in medico-legal litigations has been observed instead. Despite the lack of evidence supporting its safety and effectiveness, this method is routinely used in the clinical practice and periodical updated guidelines to standardize the method of interpretation and proper actions are proposed. However, limitations still exist and the unavoidable consequences are the increasing rate of caesarean delivery, partly due to a defensive attitude in medical choices, and medico-legal litigations for presumed inappropriate evaluation in case of perinatal adverse event. While Obstetrics Societies are trying to "fight" the rise in caesarean section rates, intrapartum EFM tracings are taken in the court proceedings as one of the main evidences in case of adverse event. The aim of this review is to discuss the limitations of guidelines dealing with intrapartum EFM and the pathophysiological basis to assess the suspicious tracings which represent the most observed and critical issue of EFM interpretation.

Reprogramming of mouse amniotic fluid cells using a PiggyBac transposon system.

Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by forced expression of defined transcription factors using different methods. Amniotic fluid (AF) cells are easy to obtain from routinely scheduled procedures for prenatal diagnosis and iPS cells have been generated from human AF. Here, we generated iPS cells from mouse AF cells, using a non-viral-based approach constituted by the PiggyBac (PB) transposon system. All iPS cell lines obtained exhibited characteristics of pluripotent cells, including the ability to differentiate toward derivatives of all three germ layers in vitro and in vivo.

Origins and genetic diversity of British cattle breeds in Brazil assessed by pedigree analyses.

Pedigree information available for Angus (ANG), Devon (DEV), Hereford (HER), and Shorthorn (SHO) cattle in Brazil was analyzed to appraise the genetic diversity and population structure of these breeds. Pedigree records collected from the beginning of the 20th century until 2010 were used in the analyses. Over time, the number of herdbook registrations declined in HER after a peak in the 1970s, remained low in DEV and SHO, and increased steadily in ANG since the 1990s, such that it the latter is now the leading British cattle breed in Brazil. The average number of offspring registered per sire ranged from about 12 (SHO) to 20 (DEV) and the mean generation interval ranged from about 6.0 (HER and SHO) to 6.4 (ANG) years. In the reference population (calves born in 2009 and 2010, plus those born in 2008 for SHO) the mean equivalent number of generations known ranged from about 7 (SHO) to 9 (HER). In the 4 breeds studied, nearly all animals born over the last few years are inbred, even though the mean level of inbreeding in the reference population is below 4% in all breeds. The rate of inbreeding per generation, computed from the individual increase in inbreeding, ranged from about 0.2 (ANG) to 0.5% (DEV), with a corresponding effective population size of 245 and 92, respectively, which is above the recommended minimum critical threshold. The number of founders/ancestors contributing with 50% of the reference population gene pool was 211/26 for ANG, 41/14 for DEV, 164/25 for HER, and 79/10 for SHO, with effective number of founders/ancestors/founder genomes of 470/68/36, 89/33/16, 289/59/30, and 200/28/18 for ANG, DEV, HER, and SHO, respectively. The genetic contribution of different countries to the gene pool of each breed indicated that, throughout the period studied, DEV genes originated predominantly from the United Kingdom, while for the other breeds there was a changing pattern over time. Until the 1970s Argentina was the major supplier of ANG, while HER and SHO genes were mostly from Uruguay, but since then the United States took the leading role as supplier of ANG, HER, and SHO genes to Brazil. Our results reveal a mild increase in inbreeding in all breeds studied, with effective population size estimates indicating that reasonable levels of genetic diversity have been maintained in all 4 breeds. Continuous monitoring of inbreeding trends and of parameters derived from probability of gene origin should be ensured to warrant the long-term maintenance of genetic diversity.

Klebsiella pneumoniae harbouring OXA-48 carbapenemase in a Libyan refugee in Italy.

A carbapenem-resistant Klebsiella pneumoniae was isolated from a blood-culture of an inpatient from Libya, hospitalized in the intensive-care unit of Negrar Hospital, Italy. The clinical isolate carried the following ß-lactamase genes, bla(TEM -1), bla(SHV -11), bla(OXA -1), bla(CTX -M-15) and bla(OXA -48), respectively. The bla(OXA -48) gene was inserted in the Tn1999.2 transposon type, carried on a conjugative, 60-kilobase plasmid, that presented an L/M backbone, hosted by a multidrug-resistant ST 101 K. pneumoniae strain. Our report highlights the international transfer of bla(OXA -48) gene and the importance of screening measures of multidrug-resistant Enterobacteriaceae.

Laparoscopic ventral incisional hernia repair: evidence-based guidelines of the first Italian Consensus Conference.

PURPOSE: The laparoscopic treatment of ventral incisional hernias is the object of constant attention and is becoming increasingly widespread in the international scientific-surgical community; however, there is ample debate on its technical details and indications. In order to establish a common approach on laparoscopic ventral incisional hernia repair, the first Italian Consensus Conference was organized in Naples (Italy) on 14-15 January 2010. METHODS: The format of the Consensus Conference was freely adapted from the standards of the National Institute of Health and the Italian Health Institute. The parties involved included the followings: a Promotional Committee, a Scientific Committee, a group of Experts, the Jury Panel and a Scientific Secretariat. RESULTS: Eleven statements, regarding three large chapters on the indications, the technical details and the management of complications were drafted on the basis of literature references collected by the Scientific Committee, documents developed by the Experts, reports presented and discussed during the Consensus Conference, and discussion among the members of the Jury. CONCLUSIONS: The laparoscopic approach is safe and effective for defects larger than 3 cm in diameter; old age, obesity, previous abdominal operations, recurrence and strangulation are not absolute contraindications. Ensuring an adequate overlap, careful adhesiolysis and correct fixing of the prosthesis are among the technical details recommended. Complications and recurrences are comparable to, and in some cases, less numerous than with the open approach.

Size and dynamics of mucosal and peripheral IL-17A+ T-cell pools in pediatric age, and their disturbance in celiac disease.

Mucosal interleukin (IL)-17A-producing T cells contribute to protective antimicrobial responses and to epithelial barrier integrity; their role in celiac disease (CD) is debated. We analyzed the frequency and developmental dynamics of mucosal (intraepithelial lymphocytes (IEL)) and circulating (peripheral blood (PB)) IL-17A (T17) and/or interferon (IFN)-γ-producing (T1, T1/T17) T-cell populations in 86 pediatric controls and 116 age-matched CD patients upon phorbol myristate acetate/ionomycin or CD3/CD28 stimulation. T17 and T1/17 are physiologically present among IEL and PB populations, and their frequency is selectively and significantly reduced in CD IEL. The physiological age-dependent increase of Th17 IEL is also absent in CD, while IFN-γ-producing PB-T cells significantly accumulate with patient's age. Finally, the amplitude of IL-17A+ and IFN-γ+ T-cell pools are significantly correlated in different individuals; this relationship only applies to CD4+ T cells in controls, while it involves also the CD4- counterpart in CD patients. In conclusion, both size and dynamics of mucosa-associated and circulating IL-17A+ T-cell pools are finely regulated in human pediatric subjects, and severely disturbed in CD. The impaired IL-17A+ IEL-T pool may negatively impact on epithelial barrier efficiency, and contribute to CD mucosa damage; the disturbed dynamics of circulating IL-17A+ and IFN-γ+ T-cell pools may be involved in the extraintestinal autoimmune manifestations associated with CD.

Laparoscopic adhesiolysis: consensus conference guidelines.

AIM: Laparoscopic adhesiolysis has been demonstrated to be technically feasible in small bowel obstruction and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting and the lack of concrete evidence in the literature have called for a consensus conference to draw recommendations for clinical practice. METHODS: A literature search was used to outline the evidence, and a consensus conference was held between experts in the field. A survey of international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts. RESULTS: Recommendations concern the diagnostic evaluation, the timing of the operation, the selection of patients, the induction of the pneumoperitoneum, the removal of the cause of obstructions, the criteria for conversion, the use of adhesion-preventing agents, the need for high-technology dissection instruments and behaviour in the case of misdiagnosed hernia or the need for bowel resection. CONCLUSION: Evidence of this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency are widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons.

Reversine increases multipotent human mesenchymal cells differentiation potential.

Among different human stem cell sources, adult mesenchymal stem cells from bone marrow (BMSCs), and more recently from adipose tissues (ASCs), have shown their capability to differentiate into a variety of different cell types, including osteoblasts, adipocytes, and muscle cells. However, mesenchymal stem cell differentiation toward certain cell types (including skeletal and cardiac muscle), while shown to be achievable, still suffers of low yields and needs to be greatly improved before any therapeutic application could be foreseen. A possible way of achieving this goal is by using a chemical-pharmacological approach to increase stem cell plasticity. Along this line, we envisioned the possibility of pre-treating BMSCs and ASCs with reversine, a synthetic purine that has been shown to induce adult cells de-differentiation. In the current study we tested reversine effects on both BMSCs and ASCs to increase their differentiation toward osteoblasts, smooth and skeletal muscle cells. Reversine pre-treatment, at very low concentration (50 nM), caused a marked increase in the differentiation yields of both BMSCs and ASCs.

Cell reprogramming: a new chemical approach to stem cell biology and tissue regeneration.

Generation of pluripotent stem cells (iPSCs) from adult fibroblasts starts a "new era" in stem cell biology, as it overcomes several key issues associated with previous approaches, including the ethical concerns associated with human embryonic stem cells. However, as the genetic approach for cell reprogramming has already shown potential safety issues, a chemical approach may be a safer and easier alternative. Moreover, a chemical approach could be advantageous not only for the de-differentiation phase, but also for inducing reprogrammed cells into the desired cell type with higher efficiency than current methodologies. Finally, a chemical approach may be envisioned to activate resident adult stem cells to proliferate and regenerate damaged tissues in situ, without the need for exogenous cell injections.