Critical role of lysosomes in the dysfunction of human Cardiac Stem Cells obtained from failing hearts.

Unlabelled: The in vivo reparative potential of Cardiac Stem Cells (CSC), cultured from explanted failing hearts (E-), is impaired by cellular senescence. Moreover, E-CSC are characterized, with respect to CSC obtained from healthy donors (D-), by an arrest in the autophagic degradation. Although the lysosome plays a pivotal role in cellular homeostasis and defects of this organelle may be associated with aging and heart failure, the lysosomal function of CSC has never been investigated.

In patients with metastatic breast cancer the identification of circulating tumor cells in epithelial-to-mesenchymal transition is associated with a poor prognosis.

Background: Although recent models suggest that the detection of Circulating Tumor Cells (CTC) in epithelial-to-mesenchymal transition (EM CTC) might be related to disease progression in metastatic breast cancer (MBC) patients, current detection methods are not efficient in identifying this subpopulation of cells. Furthermore, the possible association of EM CTC with both clinicopathological features and prognosis of MBC patients has still to be demonstrated. Aims of this study were: first, to optimize a DEPArray-based protocol meant to identify, quantify and sort single, viable EM CTC and, subsequently, to test the association of EM CTC frequency with clinical data.

Second Surgery in Insular Low-Grade Gliomas.

Background: Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented.

Objective: The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery.

Methods: A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR.

Mismatch repair system in endometriotic tissue and eutopic endometrium of unaffected women.

Objective: To test the immunohistochemical staining pattern of some mismatch repair (MMR) system proteins in endometriotic tissue (ET) and eutopic endometrium.

Methods: This was a retrospective study conducted at the Pathology and Obstetrics and Gynecology Departments of the Udine University Hospital. We analyzed 528 samples obtained from 246 patients affected by endometriosis and 71 samples from 71 patients with normal endometrium.

Preliminary results from a crowdsourcing experiment in immunohistochemistry.

Background: Crowdsourcing, i.e., the outsourcing of tasks typically performed by a few experts to a large crowd as an open call, has been shown to be reasonably effective in many cases, like Wikipedia, the Chess match of Kasparov against the world in 1999, and several others.

Adipose tissue derived stem cells: in vitro and in vivo analysis of a standard and three commercially available cell-assisted lipotransfer techniques.

Introduction: Autologous fat grafting is commonly used to correct soft-tissue contour deformities. However, results are impaired by a variable and unpredictable resorption rate. Autologous adipose-derived stromal cells in combination with lipoinjection (cell-assisted lipotransfer) seem to favor a long-term persistence of fat grafts, thus fostering the development of devices to be used in the operating room at the point of care, to isolate the stromal vascular fraction (SVF) and produce SVF-enhanced fat grafts with safe and standardized protocols.

Specific mesothelial signature marks the heterogeneity of mesenchymal stem cells from high-grade serous ovarian cancer.

Mesenchymal stem/stromal cells (MSCs) are the precursors of various cell types that compose both normal and cancer tissue microenvironments. In order to support the widely diversified parenchymal cells and tissue organization, MSCs are characterized by a large degree of heterogeneity, although available analyses of molecular and transcriptional data do not provide clear evidence. We have isolated MSCs from high-grade serous ovarian cancers (HG-SOCs) and various normal tissues (N-MSCs), demonstrated their normal genotype and analyzed their transcriptional activity with respect to the large comprehensive FANTOM5 sample dataset.

Ex vivo molecular rejuvenation improves the therapeutic activity of senescent human cardiac stem cells in a mouse model of myocardial infarction.

Cardiac stem cells (CSC) from explanted decompensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired. We aimed to identify alterations in signaling pathways that are associated with CSC senescence. Additionally, we investigated if pharmacological modulation of altered pathways can reduce CSC senescence in vitro and enhance their reparative ability in vivo.

The redox function of APE1 is involved in the differentiation process of stem cells toward a neuronal cell fate.

Unlabelled: Low-to-moderate levels of reactive oxygen species (ROS) govern different steps of neurogenesis via molecular pathways that have been decrypted only partially. Although it has been postulated that redox-sensitive molecules are involved in neuronal differentiation, the molecular bases for this process have not been elucidated yet. The aim of this work was therefore to study the role played by the redox-sensitive, multifunctional protein APE1/Ref-1 (APE1) in the differentiation process of human adipose tissue-derived multipotent adult stem cells (hAT-MASC) and embryonic carcinoma stem cells (EC) towards a neuronal phenotype.

Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm.

Absolute quantification of choline-related biomarkers in breast cancer biopsies by liquid chromatography electrospray ionization mass spectrometry.

It has been repeatedly demonstrated that choline metabolism is altered in a wide variety of cancers. In breast tumours, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-compounds. This pattern is increasingly being exploited as biomarker in cancer diagnosis.

A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient's skin.

Background: Niemann Pick C (NPC) disease is a neurovisceral lysosomal storage disorder due to mutations in NPC1 or NPC2 genes, characterized by the accumulation of endocytosed unesterified cholesterol, gangliosides and other lipids within the lysosomes/late endosomes. Even if the neurodegeneration is the main feature of the disease, the analysis of the molecular pathways linking the lipid accumulation and cellular damage in the brain has been challenging due to the limited availability of human neuronal models.

Objective: The aim of this study was to develop a human neuronal model of NPC disease by inducing neuronal differentiation of multipotent adult stem cells (MASC) isolated from NPC patients.

Cardiac stem cell senescence.

Cellular senescence processes affecting tissue resident stem cells are considered, at present, an hallmark of both aging and age-related pathologies. Therefore it is mandatory to address this problem with adequate techniques that could highlight the molecular alterations associated with this complex cellular response to stressors. Here we describe methods to characterize cardiac stem cell (CSC) senescence from a molecular and functional standpoint.

Human adipose-derived stem cells for the treatment of chemically burned rat cornea: preliminary results.

Purpose: Adipose-derived stem cells (ADSC) are multipotent, safe, non-immunogenic and can differentiate into functional keratocytes in situ. The topical use of ADSC derived from human processed lipoaspirate was investigated for treating injured rat cornea.

Methods: A total of 19 rats were used.

Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and proliferation of endometriotic tissues.

In order to study survivin, matrix metalloproteinases (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor metalloproteinase-2 (TIMP-2) expression immunohistochemically in endometriotic tissues and normal endometrium, our retrospective study considered 194 patients affected by endometriosis and 71 patients with normal endometrium. Tissue microarrays were created from paraffin-embedded blocks; immunohistochemistry was used to assess protein expression. In endometriotic tissues, survivin was expressed at a higher level than in normal endometrium; its glandular expression level was higher in non-ovarian than in ovarian endometriotic tissues and lower in stromal components.

Dental pulp stem cells differentiation reveals new insights in Oct4A dynamics.

Although the role played by the core transcription factor network, which includes c-Myc, Klf4, Nanog, and Oct4, in the maintenance of embryonic stem cell (ES) pluripotency and in the reprogramming of adult cells is well established, its persistence and function in adult stem cells are still debated. To verify its persistence and clarify the role played by these molecules in adult stem cell function, we investigated the expression pattern of embryonic and adult stem cell markers in undifferentiated and fully differentiated dental pulp stem cells (DPSC). A particular attention was devoted to the expression pattern and intracellular localization of the stemness-associated isoform A of Oct4 (Oct4A).

Role of oral cyclophosphamide in the treatment of giant cell arteritis.

Objective: Glucocorticoid (GC)-related adverse events greatly contribute to the outcome in giant cell arteritis (GCA). CYC was investigated as a steroid-sparing agent in GCA.

Methods: Nineteen patients treated with CYC were retrospectively analysed.

Acellular bone colonization and aggregate culture conditions diversely influence murine periosteum mesenchymal stem cell differentiation potential in long-term in vitro osteoinductive conditions.

Periosteum contains mesenchymal stem cells (Pe-MSCs) that contribute to normal bone growth, healing, and turnover; understanding Pe-MSC capabilities may shed light over the treatment of bone defects using tissue engineering. Bone tissue regeneration needs in vitro bone precursors or stem cell coculture onto specific scaffolds but, despite extensive research in the field, very little is known about the matrix structure of the tissue-engineered tissues and the scaffold's effects on cell differentiation. To this purpose we have selected a clonal population (murine Pe-MSCs) that was seeded and differentiated onto an acellular bone scaffold.

Role of tumor associated fibroblasts in human liver regeneration, cirrhosis, and cancer.

Tumor associated fibroblasts (TAFs) are considered a microenvironmental element critical for tumor growth and progression. Experimental studies suggest that their origin could be from mesenchymal stem cells (MSCs) derived from the bone marrow. However, the role played by TAFs in cirrhosis, hepatocellular carcinoma development, and progression is largely unknown, and in vitro human models are missing.

Expression patterns of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors determined using an endometriosis tissue microarray model.

Background: The roles of cell proliferation and genomic instability in endometriosis are highly debated aspects of the pathogenesis of this disease. Aurora A and B kinases play different important roles in cell cycle control and genomic instability and have never been studied in endometriosis. The aim of this study was to compare the expression levels of Aurora kinases, Ki-67 and hormone receptor in endometriotic tissue (ET) and normal endometrium.

Adipose tissue-derived stem cell in vitro differentiation in a three-dimensional dental bud structure.

Tooth morphogenesis requires sequential and reciprocal interactions between the cranial neural crest-derived mesenchymal cells and the stomadial epithelium, which regulate tooth morphogenesis and differentiation. We show how mesenchyme-derived single stem cell populations can be induced to transdifferentiate in vitro in a structure similar to a dental bud. The presence of stem cells in the adipose tissue has been previously reported.

Transnational telepathology consultations using a basic digital microscope: experience in the Italy-Slovenjia INTERREG project "patient without borders".

Background: In recent years, a number of technological advancements started to modify the long standing appearance and functionalities of traditional optical microscopes used in Pathology and other medical fields. In fact, at present many new tools for microscopical visualization exist that are based on digital imaging, robotization, and remote communication. Such tools are typically adopted in activities ranging from education to telediagnosis to remote consultation.

Partitioning of bronchopulmonary carcinoids in two different prognostic categories by ki-67 score.

Introduction: Histological distinction between typical and atypical bronchopulmonary carcinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid.

Myocyte turnover in the aging human heart.

Rationale: The turnover of cardiomyocytes in the aging female and male heart is currently unknown, emphasizing the need to define human myocardial biology.

Objective: The effects of age and gender on the magnitude of myocyte regeneration and the origin of newly formed cardiomyocytes were determined.

Methods And Results: The interaction of myocyte replacement, cellular senescence, growth inhibition, and apoptosis was measured in normal female (n=32) and male (n=42) human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases.