Alviano F.,Diagnostic and Specialty Medicine |
Roda B.,byFlow Srl |
Rossi M.,Diagnostic and Specialty Medicine |
Rossi M.,byFlow Srl |
And 5 more authors.
Recent Patents on Regenerative Medicine | Year: 2013
Interest in stem cell separation and purification from easily accessible clinical specimens is booming due to the increase of cell therapy applications. The recovery of pluripotent or multipotent stem cells in human sources different from the embryo requires the use of effective methods of cell sorting/enrichment. Among these sources, perinatal tissues retain cells with pivotal stem cell features such as high self-renewal ability, wide differentiation potential and immunomodulatory properties. In this perspective, methods exploiting cell biophysical differences in a less dependent process of identification based on specific markers are therefore promising. These methods allow cell isolation irrespective of the broad and diversified surface antigenic panel that usually limits the ability to easily distinguish cells as in the case of mesenchymal stromal/stem cell separation. In addition, the use of non- or minimally invasive tag-less techniques might be a way to preserve stem cell features of the selected product and reduce regulatory issues related to their use in regenerative applications. In this review, non-invasive cell sorting techniques based on microfluidic systems and relevant patents are described. In particular applications of emerging separation approach, Field-Flow Fractionation (FFF), for perinatal stem cell sorting are cited. Protocols and applications based on FFF-derived techniques are detailed. © 2013 Bentham Science Publishers.
Capri M.,Diagnostic and Specialty Medicine |
Santoro A.,Diagnostic and Specialty Medicine |
Garagnani P.,CIG |
Bacalini M.G.,CIG |
And 5 more authors.
Current Vascular Pharmacology | Year: 2014
Human longevity is a complex trait in which genetics, epigenetics, environmental and stochasticity differently contribute. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts. Recently, we implemented this model by studying centenarians’ offspring and offspring of non-long lived parents. In association, during studies on many candidate genes SNPs, positively or negatively correlated with longevity have been identified. The results obtained on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a correlation between specific genetic variants combinations and the low plasma level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway on human longevity. This pathway together with mammalian target of rapamycin (mTOR) will be reviewed as being the most promising for longevity. Further, we will summarise the role of apolipoprotein E (APOE) variants in human longevity since the results of the large European project GEHA (Genetics of Healthy Aging) indicate APOE among the chromosomal loci associated with longevity. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity rather pose questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota. To fully disentangle what appears to be an endless quest, all the components of the complexity of human longevity genetics are taken into account. © 2014 Bentham Science Publishers.
Kolovou G.,Onassis Cardiac Surgery Center |
Barzilai N.,Yeshiva University |
Caruso C.,University of Palermo |
Sikora E.,Nencki Institute of Experimental Biology |
And 9 more authors.
Current Vascular Pharmacology | Year: 2014
During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Human life span is mainly dependent on environmental and genetic factors. Favourable modifications of lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare (e.g. effective vascular disease prevention) have also increased human life span. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6) Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research? Many definitions of successful ageing have been proposed, but at present there is no consensus definition. Such definitions may need to differentiate between “Longevity Syndrome” and “Exceptional Longevity”. © 2014 Bentham Science Publishers.
PubMed | Diagnostic and Specialty Medicine, University of Valencia, Marche Polytechnic University and Yeshiva University
Type: | Journal: Mechanisms of ageing and development | Year: 2016
Human aging is a lifelong process characterized by a continuous trade-off between pro-and anti-inflammatory responses, where the best-adapted and/or remodeled genetic/epigenetic profile may develop a longevity phenotype. Centenarians and their offspring represent such a phenotype and their comparison to patients with age-related diseases (ARDs) is expected to maximize the chance to unravel the genetic makeup that better associates with healthy aging trajectories. Seemingly, such comparison is expected to allow the discovery of new biomarkers of longevity together with risk factor for the most common ARDs. MicroRNAs (miRNAs) and their shuttles (extracellular vesicles in particular) are currently conceived as those endowed with the strongest ability to provide information about the trajectories of healthy and unhealthy aging. We review the available data on miRNAs in aging and underpin the evidence suggesting that circulating miRNAs (and cognate shuttles), especially those involved in the regulation of inflammation (inflamma-miRs) may constitute biomarkers capable of reliably depicting healthy and unhealthy aging trajectories.
Sazzini M.,Laboratory of Molecular Anthropology |
Sazzini M.,Center for Genome Biology |
Garagnani P.,Diagnostic and Specialty Medicine |
Garagnani P.,University of Bologna |
And 19 more authors.
Clinical and Experimental Rheumatology | Year: 2015
Objective. Behçet's disease is a multifactorial vasculitis that shows its highest prevalence in geographical areas historically involved in the Silk Road, suggesting that it might have originated somewhere along these ancient trade routes. This study aims to provide a first clue towards genetic evidence for this hypothesis by testing it via an anthropological evolutionary genetics approach. Methods. Behçet's disease variation at ancestry informative mitochondrial DNA control region and haplogroup diagnostic sites was characterised in 185 disease subjects of Italian descent and set into the Eurasian mitochondrial landscape by comparison with nearly 9,000 sequences representative of diversity observable in Italy and along the main Silk Road routes. Results. Dissection of the actual genetic ancestry of disease individuals by means of population structure, spatial autocorrelation and haplogroup analyses revealed their closer relationships with some Middle Eastern and Central Asian groups settled along the Silk Road than with healthy Italians. Conclusion. These findings support the hypothesis that the Behçet's disease genetic risk has migrated to western Eurasia in parallel with ancestry components typical of Silk Road-related groups. This provided new insights that are useful to improve the understanding of disease origins and diffusion, as well as to inform future association studies aimed at properly accounting for the actual genetic ancestry of the examined Behçet's disease samples in order to minimise the detection of spurious associations and to improve the identification of genetic variants with actual clinical relevance. © Clinical and Experimental Rheumatology 2015.
Valente S.,University of Bologna |
Alviano F.,Diagnostic and Specialty Medicine |
Ciavarella C.,University of Bologna |
Buzzi M.,University of Bologna |
And 4 more authors.
Stem Cell Research and Therapy | Year: 2014
Introduction. Regenerative medicine challenges researchers to find noncontroversial, safe and abundant stem cell sources. In this context, harvesting from asystolic donors could represent an innovative and unlimited reservoir of different stem cells. In this study, cadaveric vascular tissues were established as an alternative source of human cadaver mesenchymal stromal/stem cells (hC-MSCs). We reported the successful cell isolation from postmortem arterial segments stored in a tissue-banking facility for at least 5 years. Methods. After thawing, hC-MSCs were isolated with a high efficiency (12 × 10§ssup§6§esup§) and characterized with flow cytometry, immunofluorescence, molecular and ultrastructural approaches. Results: In early passages, hC-MSCs were clonogenic, highly proliferative and expressed mesenchymal (CD44, CD73, CD90, CD105, HLA-G), stemness (Stro-1, Oct-4, Notch-1), pericyte (CD146, PDGFR-β, NG2) and neuronal (Nestin) markers; hematopoietic and vascular markers were negative. These cells had colony and spheroid-forming abilities, multipotency for their potential to differentiate in multiple mesengenic lineages and immunosuppressive activity to counteract proliferation of phytohemagglutinin-stimulated blood mononuclear cells. Conclusions: The efficient procurement of stem cells from cadaveric sources, as postmortem vascular tissues, demonstrates that such cells can survive to prolonged ischemic insult, anoxia, freezing and dehydration injuries, thus paving the way for a scientific revolution where cadaver stromal/stem cells could effectively treat patients demanding cell therapies. © 2014 Valente et al.; licensee BioMed Central Ltd.
Fabbrini P.,University of Milan Bicocca |
Finkel K.,University of Texas Health Science Center at Houston |
Gallieni M.,University of Milan |
Capasso G.,The Second University of Naples |
And 3 more authors.
Journal of Nephrology | Year: 2016
Acute kidney injury (AKI) is a frequent complication of multiple myeloma and is associated with increased short-term mortality. Additionally, even a single episode of AKI can eventually lead to end-stage renal disease (ESRD), significantly reducing quality of life and long-term survival. In the setting of multiple myeloma, severe AKI (requiring dialysis) is typically secondary to cast nephropathy (CN). Renal injury in CN is due to intratubular obstruction from precipitation of monoclonal serum free light chains (sFLC) as well as direct tubular toxicity of sFLC via stimulation of nuclear factor (NF)κB inflammatory pathways. Current mainstays of CN treatment are early removal of precipitating factors such as nephrotoxic drugs, acidosis and dehydration, together with rapid reduction of sFLC levels. Introduction of the proteasome inhibitor bortezomib has significantly improved the response rates in multiple myeloma due to its ability to rapidly reduce sFLC levels and has been referred to as “renoprotective” therapy. As an adjunct to chemotherapy, several new extracorporeal techniques have raised interest as a further means to reduce sFLC concentrations in the treatment of CN. Whether addition of extracorporeal therapies to renoprotective therapy can result in better renal recovery is still a matter of debate and there are currently no guidelines in this field. In this positon paper, we offer an overview of the available data and the authors’ perspectives on extracorporeal treatments in CN. © 2016, Italian Society of Nephrology.
PubMed | S. Orsola Malpighi University Hospital, Marche Polytechnic University, Urbino University, Diagnostic and Specialty Medicine and 6 more.
Type: | Journal: Aging cell | Year: 2016
To understand why livers from aged donors are successfully used for transplants, we looked for markers of liver aging in 71 biopsies from donors aged 12-92years before transplants and in 11 biopsies after transplants with high donor-recipient age-mismatch. We also assessed liver function in 36 age-mismatched recipients. The major findings were the following: (i) miR-31-5p, miR-141-3p, and miR-200c-3p increased with age, as assessed by microRNAs (miRs) and mRNA transcript profiling in 12 biopsies and results were validated by RT-qPCR in a total of 58 biopsies; (ii) telomere length measured by qPCR in 45 samples showed a significant age-dependent shortage; (iii) a bioinformatic approach combining transcriptome and miRs data identified putative miRs targets, the most informative being GLT1, a glutamate transporter expressed in hepatocytes. GLT1 was demonstrated by luciferase assay to be a target of miR-31-5p and miR-200c-3p, and both its mRNA (RT-qPCR) and protein (immunohistochemistry) significantly decreased with age in liver biopsies and in hepatic centrilobular zone, respectively; (iv) miR-31-5p, miR-141-3p and miR-200c-3p expression was significantly affected by recipient age (older environment) as assessed in eleven cases of donor-recipient extreme age-mismatch; (v) the analysis of recipients plasma by N-glycans profiling, capable of assessing liver functions and biological age, showed that liver function recovered after transplants, independently of age-mismatch, and recipients apparently rejuvenated according to their glycomic age. In conclusion, we identified new markers of aging in human liver, their relevance in donor-recipient age-mismatches in transplantation, and offered positive evidence for the use of organs from old donors.