0000000000449951
AUTHOR
Giampiero La Rocca
Isolation and phenotypical characterization of mesenchymal stem cells from the Wharton's jelly of pre-term human umbilical cord.
The balance of HSPs expression during pregnancy: the role of placenta
Wharton's Jelly Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes
New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity.
In recent years, human mesenchymal stem cells (MSC) have been extensively studied. Their key characteristics of long-term self-renewal and a capacity to differentiate into diverse mature tissues favour their use in regenerative medicine applications. Stem cells can be found in embryonic and extra-embryonic tissues as well as in adult organs. Several reports indicate that cells of Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells, expressing markers of bone marrow mesenchymal stem cells (BM-MSC), and giving rise to different cellular types of both connective and nervous tissues. Wharton's jelly mesenchymal stem cells (WJ-MSC) express …
Umbilical cord revisited: from Wharton’s jelly myofibroblasts to mesenchymal stem cells
The umbilical cord (UC) is an essential part of the placenta, contributing to foetal development by ensuring the blood flow between mother and foetus. The UC is formed within the first weeks of gestation by the enclosure of the vessels (one vein and two arteries) into a bulk of mucous connective tissue, named Wharton’s jelly (WJ) and lined by the umbilical epithelium. Since their first identification, cells populating WJ were described as unusual fibroblasts (or myofibroblasts). Recent literature data further highlighted the functional interconnection between UC and the resident cells. The UC represents a reservoir of progenitor populations which are collectively grouped into MSCs (mesenchy…
CCL5(RANTES) inhibits TGFbeta1 induced collagen production in human bronchial epithelial cells by action of Smad protein
Airway epithelial cells modulate bronchial remodelling in COPD and asthma. TGF-β1 up-regulation was observed in the bronchial epithelial cells of asthmatics and COPD patients. TGF-β is involved in airways remodelling mainly acting via the Smad pathway. Increased CCL5 was also observed in bronchi of patients with severe COPD. We investigated the effects of TGF-β1 on collagen type I, Smad 3-4 and 7 expression and the effects of CCL5 on TGF-β1-induced collagen production in human bronchial epithelial cells (16HBE).Cells were treated with 10ng/ml of TGF-β1, 10ng/ml of CCL5 and 10ng/ml of both TGF-β1 and CCL5 for 0,3 and 24 hours.TGF-b1 increased Smad3,Smad4 and collagen type I(p=0.0472, p=0.043…
Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts
Abstract Background Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD.…
Extended characterization of human umbilical cord matrix mesenchymal stem cells: expression of novel markers, immunoregulatory molecules, and differentiating potency.
ISOLATION AND PHENOTYPICAL CHARACTERIZATION OF MESENCHYMAL STEM CELLS FROM PRE-TERM HUMAN UMBILICAL CORD MATRIX
The many lives of Hsp10: From Early Pregnancy Factor to Potential Antitumoral Agent. New Proteomic Data and a Review of the Literature Focusing on Its Immunologic Properties
Heterozygous nonsense SCN5A mutation W822X explains a simultaneous sudden infant death syndrome.
The sudden, unexpected, and unexplained death of both members of a set of healthy twins (simultaneous sudden infant death syndrome (SSIDS)) is defined as a case in which both infants meet the definition of sudden infant death syndrome individually. A search of the world medical literature resulted in only 42 reported cases of SSIDS. We report the case of a pair of identical, male, monozygotic twins, 138 days old, who suddenly died, meeting the full criteria of SSIDS and where a genetic screen was performed, resulting in a heterozygous nonsense SCN5A mutation (W822X) in both twins. Immunohistochemistry was performed on cardiac tissue samples utilizing polyclonal antibodies anti-Na+ CP type V…
Flavonoids against the SARS-CoV-2 induced inflammatory storm
The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out …
Hsp60 and Hsp10 as antitumour molecular agent.
Hsp60 and Hsp10 as antitumour molecular agents
The molecular chaperones Hsp60 and Hsp10 are, according to recent reports, involved in cancer development and progression. We, for instance, have found that their expression varies with distinctive patterns in different malignancies: they are overexpressed in colorectal, exocervical and prostate carcinogenesis, and colorectal cancer progression, but they are downregulated during bronchial carcinogenesis. There is also evidence showing that Hsp60 and Hsp10 can be used as therapeutic agents, for example in rheumatoid arthritis. In view of these findings we want now to call attention to the potential of Hsp60 and Hsp10 in cancer therapy.
Modulation of MMP-2 activity in human lung fibroblasts by sigarette smoke: role in the maintenance of the inflamed state in COPD.
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.
BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …
Recent patents and advances in hepatocyte-like cells differentiation by mesenchymal stem cells
Chronic liver diseases constitute one of the main causes of death in western countries. Orthotopic liver transplantation still remains the final therapeutic approach to these diseases, but alternative therapeutic strategies are actively researched. Hepatocyte transplantation is considered a promising approach, even if this technique presents many limitations. These factors boosted the research for alternative cell sources to derive functional hepatocytes. In the last years, research on basic biology and differentiative ability of adult, embryonic and perinatal stem cells has constantly increased. The term "perinatal" indicates stem cell populations derived from foetal sources such as placen…
Hepatocyte-like cells differentiated from Wharton's jelly mesenchymal stem cells: functional characterization and expression of immunomodulatory molecules.
Evaluation of hsp60, procaspase-3 and p53 expression after oxydative stress in H292 cells
Extended characterization of hypoimmunogenic mesenchymal stem cells isolated from the subendocardial layer of human hearts from chronic heart failure patients
Purpose: Mesenchymal stem cells (MSC) are pluripotent cells which are known to reside in a number of adult organs. In human heart, various populations of stem/progenitor cells have been isolated by different groups. Several efforts still need to be made to better characterize resident or migrating MSC populations in terms of markers expression and immunogenic potential prior to their use for regenerative medicine applications in heart diseases. Methods: MSC were isolated from the sub-endocardial layer of left ventricle sections of hearts explanted from patients affected by chronic heart failure (CHF). The expression of several markers characteristic of the MSC lineage was assessed at both t…
BENIGN GASTRIC POLYPS AND HELICOBACTER PYLORI INFECTION.
Recent Patents on Oxidative Stress-Related Biomarkers in Chronic Heart Failure: The Central Role of Endothelium and Myeloperoxidase
Endothelial cells are key modulators of multiple physiological processes, and their impairment may result in the generation of endothelial dysfunction and ultimately cardiovascular diseases. Under physiologic conditions, reactive oxygen and nitrogen mediators of endothelial cells act to propagate signals driven by different stimuli, by forming molecules with a longer half-life like hydrogen peroxide. Reactive oxygen species (ROS) are constantly produced as a consequence of aerobic metabolism. Under physiologic conditions, their tendency to cause oxidative damage is counterbalanced by the action of antioxidants or oxidant-scavenging enzymes. An imbalance in favour of oxidants leads to oxidat…
Isolation and characterization of pluripotent cells from the subendocardial layer of human hearts from chronic heart failure.
Purpose: Several literature reports indicated the existence of pluripotent cells residing into the heart wall, even if in vivo heart regeneration is still a poorly comprised phenomenon. Post-infarct chronic heart failure is a pathology for which heart transplant remains a key option of clinical intervention. The amount of data collected in recent years forces researchers to better characterize the properties of adult stem cells, especially for those isolated from heart. Methods: We developed a new protocol to obtain, from the subendocardial layer of post-infarct hearts explanted from chronic heart failure patients undergoing heart transplantation, populations of mesenchymal stem cells. The …
Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative disorders.
Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent…
Role of oxidative and nitrosative stress biomarkers in chronic heart failure
In this review, we present recent insights on chronic heart failure (CHF) and the potential role of tumor necrosis factor (TNF)-alpha, interleukins, myeloperoxidase (MPO), and nitrosative stress in the progression of this disease process. Reactive oxygen species (ROS) are produced as a consequence of aerobic metabolism. Under physiologic conditions, their unfavourable effect in causing oxidative damage is counteracted by antioxidants. An imbalance in favour of oxidants leads to oxidative stress, and contributes to myocyte apoptosis, direct negative inotropic effects, and reduced bioavailability of nitric oxide (NO). Together, these effects lead to impaired vasodilatation of the coronary, pu…
Cigarette smoke affects heat-shock proteins in human lung fibroblasts: a proteomic study and identification of three expressed HSP10 variants differentially affected by the stressor
Isolation, characterization, differentiative properties of human mesenchymal stem cells isolated from the sub-endocardial layer of post-infarct chronic heart failure-affected patients
Mesenchymal stem cells (MSC) are pluripotent cells which reside in several adult organs, including heart, even if heart regeneration in vivo is still a poorly comprised phenomenon. Contrasting literature reports suggest that several efforts should be made to better characterize resident or migrating MSC populations (for both markers expression and immunogenic potential) prior to their effective use for regenerative medicine applications in heart diseases. We developed a new protocol to obtain human sub-endocardial MSC (HSE-MSC) from post-infarct hearts explanted from chronic heart failure (CHF) patients undergoing heart transplantation. We characterized HSE-MSC by immunocytochemistry (ICC) …
Characterization of the in vitro immunomodulatory properties of mesenchymal stem cells isolated from Wharton's jelly: new actors at play
Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells
Abstract: End-stage liver diseases are one of the leading causes of death in the world. Often orthotopic liver transplantation represents the final therapeutic choice. The limits of this approach are the scarcity of donor livers available, and the many side effects related to the administration of immune suppressants to the patients. Cellular therapy for liver diseases is increasingly being viewed as a promising strategy to provide hepatocytes to replenish the parenchymal cells of the organ. This technique suffers of some important limitations, such as the difficulty in isolating sufficient cell numbers (e.g. when adult or foetal hepatocytes are used for transplantation), the limited viabil…
A multipronged approach to unveil the emerging role of Hsp60 in chronic obstructive pulmonary disease
Inflammation is a major component of chronic obstructive pulmonary disease (COPD) and its cause and mechanisms are still incompletely understood. For example, the role of heat shock proteins (Hsps), many of which are molecular chaperones, has not been explored in detail in COPD, despite the fact that these molecules are known to participate in inflammation in other diseases. It has been shown that extracellular Hsps can signal certain types of T cells, macrophages, dendritic cells, and neutrophils and, thereby, elicit inflammation and immunity. However, these phenomena have not been investigated in COPD despite: a) the increasing awareness of Hsp participation in inflammation and immunity; …
Increased nitrotyrosine plasma levels in relation to systemic markers of inflammation and myeloperoxidase in chronic heart failure
The presence of a reciprocal link between inflammation and oxidative/nitrosative stress has been postulated in chronic heart failure (CHF). We aimed to determine signs of nitrosative stress in serum/plasma of CHF patients. ELISA tests were used for quantification of serum/plasma levels of Nitrotyrosine (NT), H(2)O(2), total NO, nitrite (NO(2)(-)), myeloperoxidase (MPO), Tumor Necrosis Factor-alpha (TNFalpha) and pro-Brain Natriuretic Peptide (proBNP) in 66 CHF patients (9 in NYHA I, 34 NYHA II, 23 NYHA III) and in 14 age-matched healthy subjects. NT levels were higher in NYHA III CHF patients compared to NYHA II (p<0.05), NYHA I (p<0.03) and controls (p<0.02), whereas NO(2)(-) and total NO …
ANALYSIS OF THE EFFECT OF CSE EXPOSURE ON THE EXPRESSION OF MMPS IN PULMONARY EPITHELIAL CELL LINES
Wharton's jelly mesencymal stem cells differentiated into hepatocyte-like cells show expression of immunomodulatory molecules
Isolation and phenotypical characterization of mesenchymal stem cells from the Wharton's jelly of pre-term human umbilical cord
CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome.
AIMS: CD1a is a molecule belonging to the highly conserved group of CD1 proteins. Its expression in dendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently, the development of a successful antitumour response. The aim was to investigate the presence of CD1a+ cells in both primary tumours and lymph nodes (LN) of a series of 35 invasive ductal carcinomas by both immunohistochemistry and reverse transcription-polymerase chain reaction. METHODS AND RESULTS: CD1a antigen was more expressed in N0 than N1 breast cancer (P < 0.0001) in both primary lesions and LN metastases and correlated positively and significantly with oestrogen (ER) (P =…
The role of intrinsic pathway in apoptosis activation and progression in Peyronie's Disease.
Peyronie’s disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunos…
Expression of CD1a by Barrett’s metaplasia epithelial cells
Perinatal stem cells patents and applications: Regenerative medicine, tissue repair, immune modulation
CD1a expression in Barrett’s oesophagus: new role for an old molecule against metaplastic progression
ISOLATION AND CHARACTERIZATION OF CD276+/HLA-E+ HUMAN SUB-ENDOCARDIAL MESENCHYMAL STROMAL CELLS FROM CHRONIC HEART FAILURE PATIENTS: ANALYSIS OF DIFFERENTIATION CAPACITY AND IMMUNOMODULATORY MARKERS EXPRESSION.
Stenosi del giunto pielo-ureterale unilaterale congenita: identificazione di biomarcatori, valutazione clinico-strumentale del danno renale e correlazione con il dato istologico.
Stenosi del giunto pielo-ureterale, biomarcatori urinari, fibrosi, funzione renale, matrice extracellulare.
Editorial - Connecting the Dots: The Promises of Wharton's Jelly Mesenchymal Stem Cells for Tissue Repair and Regeneration
Mesenchymal stem cells (MSC) constitute a variety of cellular populations which were described first about 35 years ago in the bone marrow (BM) stroma [1]. These years have foreseen an exponential increase of reports pointing out features, stemness, markers, tissue sources and clinical applications of these cells. Cells with MSC features can be isolated from virtually every adult organ in the body, as well from a group of fetus-associated sources (cells derived from the latter tissues are collectively known as perinatal stem cells) [2]. In recent years, the umbilical cord arose as a promising source of mesenchymal stem cells, which can be isolated in relatively high numbers (compared to BM)…
Cross-talk between fibroblast and breast cancer cells: a proteomic study
Wharton’s Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro
Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of i…
ADULT STEM CELLS: THE REAL ROOT INTO THE EMBRYO?
During embryonic development, a pool of cells may become a reserve of undifferentiated cells, the embryo-stolen adult stem cells (ESASC). ESASC may be responsible for adult tissue homeostasis, as well as disease development. Transdifferentiation is a sort of reprogramming of ESASC from one germ layer-derived tissue towards another. Transdifferentiation has been described to take place from mesoderm to ectodermal- or endodermal-derived tissues and viceversa but not from ectodermal- to endodermal-derived tissues. We hypothesise that two different populations of ESASC could exist, the first ecto/mesoblast-committed and the second endo/mesoblast-committed. If confirmed, this hypothesis could le…
Hsp10 beyond mitochondria: novel locations predict as yet undescribed roles
New frontiers in regenerative medicine in cardiology: the potential of Wharton's jelly mesenchymal stem cells.
Cardiomyopathies are still the first cause of death in the world. The identification of resident stem cells, comprising those derived from sub-endocardial stroma, suggests the possible self regeneration of the heart under autocrine/paracrine modulation in the cardiac microenvironment. Nevertheless, because of the limited in vivo regeneration potential of damaged cardiac tissue, the use of drugs and ultimately cardiac transplantation remain the common treatments of heart diseases and defects. The differentiative potential of embryonic and mesenchymal stem cells (MSCs) derived from different tissues (such as bone marrow and adipose tissue) was extensively explored in cell therapy for regenera…
CD1a expression in primary breast cancer and lymph nodes: correlation with clinicopathological parameters.
Wharton’s jelly mesenchymal stem cells differrentiation towards hepatocyte-like cells: in vitro evidences
Shifting back the fetomaternal interface: WHarton's jelly mesenchymal stem cells immunomodulatory molecules and their journey from umbilical cord to differentiated cells.
EVALUATION OF HSP60, PROCASPASE-3 AND p53 EXPRESSION AFTER OXYDATIVE STRESS IN NCI-H292 CELLS
Wharton's jelly immunomodulatory properties and unique markers expression: new actors at play
Caffeine and cardiovascular diseases: critical review of current research.
Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistica…
Mesenchymal Stromal Cells From Wharton's Jelly (WJ-MSCs)
Abstract Among the potential sources of cells with attractive features for regenerative medicine, perinatal tissues have gained much attention in recent years. The umbilical cord (UC) is a fundamental part of placenta, the organ providing feto–maternal interface during pregnancy. The mature UC is constituted by three vessels, one vein, and two arteries, which are comprised into a meshwork formed by a mature mucous connective tissue, named Wharton's jelly (WJ). Recent data from research groups worldwide highlighted that WJ stromal cells possess unique features both in terms of differentiative ability and immunomodulation. These features are desirable for cellular therapy applications, thereb…
Umbilical cord versus bone marrow-derived mesenchymal stromal cells.
incetheplacentaisapostnatal tissue and discarded asmedical waste, harvesting stem cells from this organrepresents a noninvasive and ethically conductive proce-dure. Perinatal stem cells isolated from amnion, chorion,umbilical cord, and cord blood are increasingly viewedas reliable sources of mesenchymal stromal cells (MSCs)alternative to bone marrow-derived ones (BM-MSCs),which are currently the most commonly used in clinicalapplications [1–5].Perinatal stem cells are a bridge between embryonic stemcells (ESCs) and adult stem cells (such as BM-MSCs). Theyshare many characteristics of both cells [1,6]. Considering thestructural complexity of the term ‘‘placenta,’’ we have fo-cused our attent…
Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure.
Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 mic…
Wharton's Jelly Mesenchymal Stem Cells and Immune Modulation: Regenerative Medicine Meets Tissue Repair
Recent patents and advances on isolation and cellular therapy applications of mesenchymal stem cells from human umbilical cord Wharton's jelly
In recent years, important advances were made to clarify the biology and potential use of mesenchymal stem cells (MSC) in the therapy of a number of disorders. MSC are present in a number of tissues, ranging from adult bone marrow, to several adult organs, adipose tissue and, in the last years, the fetal-associated (also named as extraembryonic) tissues (e.g. placenta, amniotic membrane, umbilical cord). In particular, research on cells derived from mature umbilical cord, a tissue which is still discarded at birth, showed that mesenchymal stem cells can be successfully isolated from the Wharton’s jelly (WJ), the main constituent of this organ. This review will take in to account the patents…
At the roots of tolerogenicity and immune modulation: an in vitro and in situ survey on the expression of immunomodulatory molecules by Wharton’s jelly mesenchymal stem cells.
Extending the usefulness of extraembryonic mesenchymal stem cellsin regenerative medicine: expression of novel markers, immunoregulatory molecules, and novel differentiation capacities.
Mesenchymal stem cells (MSC) are considered promising tools in regenerative medicine applications. Even if they are already applied clinically, their extended characterization is being increasingly viewed as a needed feature, in order to avoid contrasting results when translating “in vitro” experiments to “in vivo” approaches. We recently demonstrated in human MSC isolated from the umbilical cord matrix (HEMSC) the expression of novel markers indicative of their stemness, as well as differentiative and immune properties [1]. HEMSC were cultured and subject to multiple molecular and morphological analyses to determine the expression of markers of interest. Undifferentiated HEMSC expressed im…
BENIGN GASTRIC POLYPS AND HELICOBACTER PYLORI
Expression of CD1a by Barrett’s metaplasia epithelial cells.
Two isoelectric variants of HSP10 are down-regulated by cigarette smoke exposure in airway cells: A Proteomic study
Cigarette smoke exposure affects expression and extracellular activity levels of gelatinase A and B in airway epithelial cells
Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers
The presence of multipotent cells in several adult and embryo-related tissues opened new paths for their use in regenerative medicine. Extraembryonic tissues such as umbilical cord are considered a promising source of stem cells, potentially useful in therapy. The characterization of cells from the umbilical cord matrix (Wharton''s Jelly) and amniotic membrane revealed the presence of a population of mesenchymal-like cells, sharing a set of core-markers expressed by "mesenchymal stem cells". Several reports enlightened the differentiation capabilities of these cells, even if at times the lack of an extensive characterization of surface markers and immune co-stimulators expression revealed h…
The effect of Betanin parenteral pretreatment on Jejunal and pulmonary tissue histological architecture and inflammatory response after Jejunal ischemia-reperfusion injury
Intestinal ischemic-reperfusion (IR) injury has detrimental effects on both local and distant organs in the body. Betanin is known for its antioxidant properties, and it is found mostly in vegetables. Therefore, the aim of the present study was to test the hypothesis that betanin administration prior intestinal IR, may be beneficial in protecting jejunal mucosa and lung parenchyma against IR damage. Male specific pathogen-free Charles River Wistar rats were used (n = 42). Betanin (50 mg/kg) was administered intraperitoneally 30 min before ischemia of the superior mesenteric artery lasting 1 h, followed by 1, 4 and 24 h of reperfusion. Immunohistochemical as well as histomorphometrical analy…
Downregulation of myogenic microRNAs in sub-chronic but not in sub-acute model of daunorubicin-induced cardiomyopathy
Cardiac muscle-related microRNAs play important roles in cardiac development and disease by translational silencing of mRNAs, the dominant mechanism of microRNA action. To test whether they could be involved in daunorubicin-associated cardiomyopathy (DACM), we determined expression patterns of myomiRs in two distinct models of DACM. We used 10â12 weeks old male Wistar rats. In the sub-acute model, rats were administered with six doses of daunorubicin (DAU-A, 3Â mg/kg, i.p., every 48Â h). Rats were sacrificed two days after the last dose. In the sub-chronic model, anaesthetized rats were administered a single dose of daunorubicin (15Â mg/kg, i.v., DAU-C). Age-matched controls (CON) receive…
Perinatal and Wharton's jelly-derived mesenchymal stem cells in cartilage regenerative medicine and tissue engineering strategies
Stem cells can be found in embryonic and extraembryonic tissues as well as in adult organs. In particular, research in the last few years has delineated the key features of perinatal stem cells derived from fetus-associated tissues. These cells show multiple differentiation potential, can be easily expanded ex vivo, and raise no ethical concerns as regards their use. Several reports indicate that cells isolated from Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells that express markers shared by other mesenchymal stem cells (MSC) and give rise to different mature cell types belonging to all three germ layers. Moreover, WJ-MSC display…
A novel isolation technique and extended characte-rization of mesenchymal stem cells from human umbilical cord matrix: disclosing new potentials for regenerative medicine applications.
Oxidative stress induces myeloperoxidase expression by HUVEC and chronic heart failure endocardial endothelial cells. Active contribution of endothelium to an inflammatory heart disease.
Role of videoassisted thoracoscopy procedure in the diagnosis and treatment of malignant pleural mesothelioma
Characterization of the immunomodulatory properties of mesenchymal stem cells isolated from Wharton's jelly
In vitro and in vivo detection of end-products of MPO-driven oxidative and nitrosative stress in human endocardial endothelial cells from patients affected by chronic heart failure
Immunohistochemical marker for Na+ CP type Vα (C-20) and heterozygous nonsense SCN5A mutation W822X in a sudden cardiac death induced by mild anaphylactic reaction
A sudden death likely due to mild anaphylactic reaction in a young man is described. Autoptic, histologic, immunohistochemical, and laboratory findings were strongly consistent with the diagnosis of a mild anaphylactic reaction. Genetic molecular analysis, performed on formalin-fixed, paraffin-embedded tissues, showed a mutation described as W822X in a family with electrocardiographic pattern typical of Brugada Syndrome. It results in a nonsense mutation generating a truncated form of the channel protein. The mutation is due to a point substitution of a guanine with an adenine residue (G2466A). Immunohistochemistry and laser scanning confocal microscopy on sections from heart formalin-fixed…
Human HSP10 variants downregulation after cigarette smoke extract exposure in lung cells
The impact of cigarette-smoke stress (a form of oxidative stress) on human lung fibroblasts and epithelial cells, particularly its effect on Hsp10 expression, has not been characterized despite the fact that a role for mitochondrial chaperonins in the development of lung diseases, ranging from chronic obstructive pulmonary disease to bronchial carcinogenesis, has been suggested (1). We studied the effects of non-lethal doses of cigarette smoke extract (CSE) on the expression of Hsp10 in human lung fibroblasts (HFL-1 line) and epithelial cells (16HBE line). Proteomics was carried out using 2D-IPG, silver stain, western blotting, and mass-spectrometry; mRNA was measured by RT-PCR. Database se…
Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications.
Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of pare…
Isolation and characterization of human extraembryonal mesoderm mesenchymal stem cells from umbilical cord
Divided at birth: an in vitro and in situ survey on the expression of immunomodulatory molecules in human Wharton's jelly mesenchymal stem cells and paired umbilical cords
Involvement of gelatinases in breast cancer: correlation with clinical parameters and 2D-IPG applications.
Energy Metabolism Analysis of Three Different Mesenchymal Stem Cell Populations of Umbilical Cord Under Normal and Pathologic Conditions
AbstractHuman umbilical cord mesenchymal stem cells (hUC-MSCs) are a pivotal source of therapeutically active cells for regenerative medicine due to their multipotent differentiation potential, immunomodulatory and anti-inflammatory proprieties, as well as logistical collection advantages without ethical concerns. However, it remains poorly understood whether MSCs from different compartments of the human umbilical cord are therapeutically superior than others. In this study, MSCs were isolated from Wharton’s jelly (WJ-MSCs), perivascular region (PV-MSCs) and cord lining (CL-MSCs) of hUC. These cells expressed the mesenchymal markers (CD90, CD73), stemness marker (OCT4), endothelial cell adh…
Atrial Natriuretic Factor Downregulation during Breast Cancer Progression
TGFbeta signaling: roles of Smads
CIGARETTE SMOKE AFFECTS HEAT-SHOCK PROTEINS IN HUMAN LUNG FIBROBLASTS: A PROTEOMIC STUDY AND IDENTIFICATION OF THREE EXPRESSED HSP10 VARIANTS DIFFERENTIALLY AFFECTS BY STRESSOR.
Effect of a pathogenic stressor on human HSP10.
Wharton's Jelly Mesenchymal Stromal Cells as a Feeder Layer for the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells: a Review
In recent years, umbilical cord blood (UCB) has been widely used as an alternative source to bone marrow (BM) for transplantation of hematopoietic stem and progenitor cells (HSPCs) in a variety of hematological and non-hematological disorders. Nevertheless, the insufficient number of UCB-HSPCs for graft represents a major challenge. HSPCs ex vivo expansion prior to transplantation is a valid strategy to overcome this limit. Several attempts to optimize the expansion conditions have been reported, including the use of mesenchymal stromal cells (MSCs) as feeder layer. Wharton's Jelly (WJ), the main component of umbilical cord (UC) matrix, is especially rich in MSCs, which are considered ideal…
Wharton's jelly mesenchymal stem cells differentiation towards hepatocyte-like cells: functional characterization and expression of immunomodulatory molecules
Oxidative stress-driven expression of myeloperoxidase in endothelial cells results in accumulation of markers of oxidative and nitrosative stress in vitro and in vivo
Endothelial cells (ECs), are able to manage with higher concentrations of ROS as well as reactive nitrogen species, respect to the other cell types. The unbalance between oxidizing species and antioxidant cellular defences has been implicated in the pathogenesis of cardiovascular diseases. While the role of MPO in the oxidative burst is well established, the effects of this enzyme on endothelial biology have only recently come to light. MPO can interact with endothelial –derived NO causing its depletion and favouring its conversion to nitrogen dioxide radical, a compound responsible of protein nitration generating 3-nitrotyrosine. Moreover, MPO is the only enzyme capable to form hypoclorous…
Wharton's jelly mesenchymal stem cells differentiation towards hepatocyte-like cells: functional characterization and expression of immunomodulatory molecules.
Telomerase activity and telomeric states in cell proliferative and differentiative mechanisms.
Telomeres are DNA-protein complexes playing an important role in the maintenance of genome integrity. Telomerase is the enzyme acting as a template for addition of new telomeric repeats; this addition is essential for those cellular populations that have proliferative and differentiative potential. Telomerase and associated proteins are essential in response to DNA damage. Moreover, telomere-associated proteins as TRF2 are involved in all signalling transduction pathway which drive cellular proliferation and differentiation. In somatic cells, shortening of telomeres contributes to the onset of senescence or apoptosis; tissues which require cellular renewal express telomerase activity in ord…
Chaperones in disease: quantitative changes in chronic obstructive pulmonary disease (COPD)
Role of TGF-b1 in type I collagen production in bronchial epithelial cells: effects on Smad7 inhibitory role?
Airway epithelial cells play an important role in inflammatory, apoptotic and remodelling process associate with fibrosis and COPD. Transforming growth factor 1 (TGF-b1) is involved in airways remodelling by Smads signalling pathway. We investigated the role of TGF-b1 on type I collagen production and Smads (Smad 2-3-4-and 7) expression in bronchial epithelial cells (16HBE). Cells were treated with 1ng/ml and 10ng/ml of TGF-b1 for 0, 3 and 24 hours. With low dose of TGF-b1 we observed no significant variation on Smad2 mRNA expression for both times but a significant increased of Smad7 mRNA expression at 3h (p=0.0043) and a significant reduction of Smad3, Smad4 and Smad7 mRNA expression at 2…
Zymographic analysis of circulating and tissue forms of colon carcinoma gelatinase A (MMP-2) and B (MMP-9) separated by mono- and two-dimensional electrophoresis.
Gelatinase A (MMP-2) and gelatinase B (MMP-9) play a key role in the proteolytic cascade leading to ECM degradation during invasion and metastasis. The enzyme activity is regulated both at the intra- and extra-cellular level. Extracellular regulation is achieved mainly through the balance between proenzyme activation and inhibition, which appears to be altered in cancer patients. One of the mechanisms of MMP inhibition is the binding of the enzymes to appropriate tissue inhibitors (TIMP). In the recent literature, it has been suggested that MMP-2 and/or MMP-9 are indeed over-produced in many carcinomas, while the identity of the various enzymatic forms (latent, activated and enzyme/inhibito…
Novel Immunomodulatory Markers Expressed by Human WJ-MSC: an Updated Review in Regenerative and Reparative Medicine.
Mesenchymal (stromal) stem cells (MSC) are a broad class of stromal populations which are able to differentiate towards mature cell types, and do express molecules involved in immune modulation, tolerance induction and inflammation dampening. MSC can be virtually isolated from each adult organ, as well as from foetus-associated perinatal tissues. In particular, Wharton's jelly-derived MSC (WJ-MSC) bear all of these key properties, together with their ease of sourcing and lack of ethical issues. Cellular therapy is a key technique in regenerative medicine approaches, in particular for the treatment of diseases in which physiological processes of cellular repopulation are blocked by the under…
Hydrogen peroxide in endothelium: multifaceted roles in cellular stress and signalling.
Cigarette smoke exposure downregulates two isoelectric variants of human HSP10 in airway epithelial cells: A Proteomic study
Non-classical type I HLAs and B7 costimulators revisited: analysis of expression and immunomodulatory role in undifferentiated and differentiated MSC isolated from human umbilical cord Wharton's jelly
Introduction. Wharton’s jelly (WJ), the main constituent of umbilical cord, emerged as a reliable and uncontroversial source of mesenchymal stem cells (MSC). WJ-MSC show unique ability in crossing lineage borders, therefore being capable to trans-ifferentiate towards mature cytotypes derived from the three germ layers. As other fetal-associated cells, WJ-MSC express several immunomodulatory molecules, essential during the initial phases of human development and for the processes linked to the tolerance of the mother to the semiallogeneic embryo. Very few data are present in literature on the maintenance of the immune privilege of the naïve cells after performing differentiation. Our previou…
Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin
Heat-shock protein (Hsp)10 is the co-chaperone for Hsp60 inside mitochondria, but it also resides outside the organelle. Variations in its levels and intracellular distribution have been documented in pathological conditions, e.g. cancer and chronic obstructive pulmonary disease (COPD). Here, we show that Hsp10 in COPD undergoes changes at the molecular and subcellular levels in bronchial cells from human specimens and derived cell lines, intact or subjected to stress induced by cigarette smoke extract (CSE). Noteworthy findings are: (i) Hsp10 occurred in nuclei of epithelial and lamina propria cells of bronchial mucosa from non-smokers and smokers; (ii) human bronchial epithelial (16HBE) a…
CD1a and antitumour immune response
Primary immune response is based on the capacity of local professional antigen-presenting cells (whose prototype is represented by dendritic cells, DCs) to take up and present antigens to selected clones of T cells, but also to non-specific effector cells such as macrophages or natural killer cells. The four CD1 proteins, all of which share a limited homology to class I MHC proteins, are differently expressed in various cell types, of both mesenchymal and, as recently described, epithelial lineage. Regarding the role of CD1 molecules in the anti-tumour response, it has been reported that CD1+ dendritic cells are involved in the first steps of the primary immune response in a number of malig…
Wharton’s jelly mesenchymal stem cells differentiation into hepatocyte-like cells: functional characterization and expression of immunomodulatory molecules
Mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) recently emerged as promising tools for cellular therapy due to their ability to differentiate into diverse cell types and their immunomodulatory features. Little is known on the expression of immunomodulatory molecules in mature cells differentiated from WJ-MSCs, therefore we aimed to characterize the extent of maintenance of the naive traits of these cells also in a highly specialized differentiated counterpart. WJ-MSCs were differentiated into hepatocyte-like cells (HLCs) with a four weeks protocol. RT-PCR, flow cytometry, IHC and ICC were performed to assess expression of key markers in both undifferentiated and differentiate…
Immune-related molecole are espresse by both naive and differentiated Wharton’s jelly mesenchymal stem cells: a new avenue for cellular therapy
Wharton’s Jelly Mesenchymal Stromal Cells Support the Expansion of Cord Blood–derived CD34+Cells Mimicking a Hematopoietic Niche in a Direct Cell–cell Contact Culture System
Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) have been recently exploited as a feeder layer in coculture systems to expand umbilical cord blood–hematopoietic stem/progenitor cells (UCB-HSPCs). Here, we investigated the role of WJ-MSCs in supporting ex vivo UCB-HSPC expansion either when cultured in direct contact (DC) with WJ-MSCs or separated by a transwell system or in the presence of WJ-MSC–conditioned medium. We found, in short-term culture, a greater degree of expansion of UCB-CD34+cells in a DC system (15.7 ± 4.1-fold increase) with respect to the other conditions. Moreover, in DC, we evidenced two different CD34+cell populations (one floating and one adherent to WJ-MSCs) with …
Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.
This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different t…
Effects of cigarette smoke on modulation of proteolytic activity in lung fibroblasts: implications for lung inflammatory diseases
Human Wharton's jelly mesenchymal stem cells maintain the expression of key immunomodulatory molecules when subjected to osteogenic, adipogenic and chondrogenic differentiation in vitro: new perspectives for cellular therapy.
Rheumatoid arthritis and osteoarthritis are the main diseases that imply an inflammatory process at the joints involving the articular cartilage. Recently, mesenchymal stem cells (MSCs) derived from perinatal tissues were considered good candidates for cellular therapy of musculoskeletal and orthopaedic diseases, since they can differentiate into multiple cell types and are an easily accessible cellular source. Therefore, several protocols exist on the differentiation of mesenchymal stem cells of different origins into osteoblasts and chondrocytes. Another key feature of MSCs is their capacity to modulate the immune system responses in vitro and in vivo. This may have critical outcomes in d…
Wharton’s Jelly Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes
Type 1 diabetes is an autoimmune disease caused by the destruction of endocrine pancreas β cells by T lymphocytes, for which genetic and environmental risk factors have been proposed. Patients require daily infusions of recombinant insulin to overcome the reduced production by their own cells, but there is an increasing demand for a permanent and efficient supplementation which could better modulate the need for the hormone during the normal activities. For this reason, transplant-based therapeutic models have been proposed such as whole organ transplantation and Langerhans islets transplantation. These techniques are limited by many factors such as the lack of donors, the risks linked to t…
Isolation and Characterization of CD276+/HLA-E+ Human Subendocardial Mesenchymal Stem Cells from Chronic Heart Failure Patients: Analysis of Differentiative Potential and Immunomodulatory Markers Expression
Mesenchymal stem cells (MSCs) are virtually present in all postnatal organs as well as in perinatal tissues. MSCs can be differentiated toward several mature cytotypes and interestingly hold potentially relevant immunomodulatory features. Myocardial infarction results in severe tissue damage, cardiomyocyte loss, and eventually heart failure. Cellular cardiomyoplasty represents a promising approach for myocardial repair. Clinical trials using MSCs are underway for a number of heart diseases, even if their outcomes are hampered by low long-term improvements and the possible presence of complications related to cellular therapy administration. Therefore, elucidating the presence and role of MS…
Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis.
BackgroundIt is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.Methods and resultsBronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between th…
Wharton's jelly mesenchymal stem cells immunomodulatory molecules: their journey from umbilical cord to differentieted cells.
Effects of oxidative stress on primary human endothelial cells. Potential active contribution of endothelium to inflammatory heart diseases
New perspectives on the roles of proteinases and lung structural cells in the pathogenesis of chronic obstructive pulmonary disease.
Role of CD1A and HSP60 in the antitumoral response of oesophageal cancer
Oesophageal cancer (OC) is one of the most common and severe forms of tumor. A wider knowledge of molecular mechanisms which lead to a normal epithelium becoming a neoplasm may reveal new strategies to improve treatment and outcome of this disease. In this review, we report recent findings concerning molecular events which take place during carcinogenesis of the oesophagus. In particular, we focus on the role of two molecules, CD1a and Hsp60, which are overexpressed in oesophageal and many other types of tumor. Both molecules may present tumor antigens and promote in situ the stimulation of an antitumoral immune activity. We suggest there is a synergistic action between these molecules. Fur…
Smoke exposure affects gelatinase A and B activity levels in two lung epithelial cell lines
Wharton’s Jelly Mesenchymal Stem Cells as Candidates for Beta Cells Regeneration: Extending the Differentiative and Immunomodulatory Benefits of Adult Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes
Mesenchymal stem cells (MSC) are uniquely capable of crossing germinative layers borders (i.e. are able to differentiate towards ectoderm-, mesoderm- and endoderm-derived cytotypes) and are viewed as promising cells for regenerative medicine approaches in several diseases. Type I diabetes therapy should potentially benefit from such differentiated cells: the search for alternatives to organ/islet transplantation strategies via stem cells differentiation is an ongoing task, significant goals having been achieved in most experimental settings (e.g. insulin production and euglycaemia restoration), though caution is still needed to ensure safe and durable effects in vivo. MSC are obtainable in …