Time filter

Source Type

Lysy P.A.,Institute Of Recherche Experimentale Et Clinique | Weir G.C.,Harvard Stem Cell Institute | Bonner-Weir S.,Harvard Stem Cell Institute
Current Diabetes Reports | Year: 2013

Cell therapy is currently considered as a potential therapeutic alternative to traditional treatments of diabetes. Islet and whole pancreas transplantations provided the proof-of-concept of glucose homeostasis restoration after replenishment of the deficiency of β cells responsible for the disease. Current limitations of these procedures have led to the search for strategies targeting replication of pre-existing β cells or transdifferentiation of progenitors and adult cells. These investigations revealed an unexpected plasticity towards β cells of adult cells residing in pancreatic epithelium (eg, acinar, duct, and α cells). Here we discuss recent developments in β-cell replication and β-cell transdifferentiation of adult epithelial pancreatic cells, with an emphasis on techniques with a potential for clinical translation. © 2013 Springer Science+Business Media New York.


Mesia K.,University of Kinshasa | Tona L.,University of Kinshasa | Mampunza M.M.,University of Kinshasa | Ntamabyaliro N.,University of Kinshasa | And 8 more authors.
Planta Medica | Year: 2012

According to the promising results of the Phase I and Phase IIA clinical trials with the herbal medicinal product PR 259 CT1 consisting of an 80 % ethanolic extract of the stem bark of Nauclea pobeguinii containing 5.6 % strictosamide, a Phase IIB study was conducted as a single blind prospective trial in 65 patients with proven Plasmodium falciparum malaria to evaluate the effectiveness and safety of this herbal drug. The study was carried out simultaneously using an artesunate-amodiaquine combination (Coarsucam®) as a positive control. This combination is the standard first-line treatment for uncomplicated malaria recommended by the National Programme of Malaria Control in the Democratic Republic of Congo (DR Congo). With regard to PR 259 CT1, patients were treated with a drug regimen of two 500-mg capsules three times daily for three days in the inpatient clinic, followed by out-patient treatment of one 500-mg capsule three times daily during the next four days; the positive control group received two tablets containing 100 mg artesunate and 270 mg amodiaquine (fixed-dose) once daily during three consecutive days. Antimalarial responses were evaluated according to the WHO 2003 guideline for a 14-day test. The results from the physical and laboratory examinations did not show any significant changes in values of vital signs, ECG, biochemical, and haematological parameters. The study showed a significant decreased parasitaemia in patients treated with PR 29 CT1 and artesunate-amodiaquine with adequate clinical parasitological responses (APCR) at day 14 of 87.9 and 96.9 %, respectively. The former product was better tolerated than the latter since more side effects were observed for the artesunate-amodiaquine combination. These results indicated that PR 259 CT1 can be considered as a promising candidate for the development of a herbal medicine for the treatment of uncomplicated falciparum malaria. © Georg Thieme Verlag KG Stuttgart · New York.


Lafosse A.,Institute Of Recherche Experimentale Et Clinique | Desmet C.,Institute Of Recherche Experimentale Et Clinique | Aouassar N.,Institute Of Recherche Experimentale Et Clinique | Andre W.,Institute Of Recherche Experimentale Et Clinique | And 6 more authors.
Plastic and Reconstructive Surgery | Year: 2015

Background: Nonhealing wounds are unable to integrate skin autografts by avascular and fibrotic dermal tissue. Adipose-derived stromal cells can improve the local environment of the wound bed by angiogenesis and immunomodulation. This work aimed to develop a biological dressing made of adipose-derived stromal cells onto a human acellular collagen matrix. Methods: Adipose-derived stromal cells were isolated from human adipose tissue (n = 8). In vitro, the genetic stability during early and late passages (1, 4, 10, and 16) and vascular endothelial growth factor (VEGF) secretion were assessed. Adipose-derived stromal cell adhesion and spreading on collagen matrix were preliminarily studied. In vivo tumorigenicity, angiogenesis, and tissue oxygenation were assessed after implantation of the construct in nude rats (n = 10). The biological dressing was manufactured and implanted in three patients with chronic wounds. Results: In vitro, aneuploidies, but no clonal transformation, were detected up to late cellular passages. VEGF was secreted more during hypoxia (0.1% oxygen) than during normoxia (21% oxygen). Adipose-derived stromal cells can adhere and spread on the scaffold within 18 to 20 days. No tumor development occurred 3 months after implantation in immunocompromised rats. Vessel counts and tissue oxygenation were higher after adipose-derived stromal cell implantation. In patients, granulation tissue was found (276 percent of vessel density), followed by epithelialization or split-thickness skin engraftment up to 22 months after implantation. Conclusions: Implantation of adipose-derived stromal cells seeded onto human acellular collagen matrix (biological dressing) represents a promising therapy for nonhealing wounds, offering improvement in dermal angiogenesis and remodeling. This therapy using autologous stromal cells is safe, without significant genetic alterations after in vitro expansion. © 2015 by the American Society of Plastic Surgeons.


Horman S.,Institute Of Recherche Experimentale Et Clinique | Beauloye C.,Institute Of Recherche Experimentale Et Clinique | Vanoverschelde J.-L.,Institute Of Recherche Experimentale Et Clinique | Bertrand L.,Institute Of Recherche Experimentale Et Clinique
Current Heart Failure Reports | Year: 2012

The AMP-activated protein kinase (AMPK) can be firstly considered as a cellular fuel gauge. AMPK rapidly senses energy deprivation and orchestrates a metabolic response to maintain an acceptable energy level required for cell survival under such adverse condition. Its protective role during myocardial ischemia has been deeply documented. More recently, it has been shown that the role of AMPK extends to several nonmetabolic effects related to other cardiac pathologies comprising diabetic cardiomyopathy, cardiac hypertrophy, and heart failure. Here, we briefly review the different roles played by AMPK in the control of cardiac metabolism and function under normal and pathological conditions. The potential cardioprotective actions of AMPK and the relative importance of its energetic and nonmetabolic effects in these mechanisms are deeply discussed. © Springer Science+Business Media, LLC 2012.


PubMed | Institute Of Recherche Experimentale Et Clinique
Type: Review | Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology | Year: 2016

Airway and intestinal epithelial layers represent first-line physical barriers, playing a key role in mucosal immunity. Barrier dysfunction, characterized by alterations such as disruption of cell-cell apical junctions and aberrant epithelial responses, probably constitutes early and key events for chronic immune responses to environmental antigens in the skin and in the gut. For instance, barrier dysfunction drives Th2 responses in atopic disorders or eosinophilic esophagitis. Such epithelial impairment is also a salient feature of allergic asthma and growing evidence indicates that barrier alterations probably play a driving role in this disease. IgA has been identified as the most abundant immunoglobulin in mucosa, where it acts as an active barrier through immune exclusion of inhaled or ingested antigens or pathogens. Historically, it has been thought to represent the serum factor underlying reaginic activity before IgE was discovered. Despite several studies about regulation and major functions of IgA at mucosal surfaces, its role in allergy remains largely unclear. This review aims at summarizing findings about epithelial functions and IgA biology that are relevant to allergy, and to integrate the emerging concepts and the recent developments in mucosal immunology, and how these could translate to clinical observations in allergy.


PubMed | Institute Of Recherche Experimentale Et Clinique
Type: Journal Article | Journal: Journal of immunology (Baltimore, Md. : 1950) | Year: 2013

We showed that IgA induces IL-10 in monocytes and dendritic cells. Because reciprocal inhibition exists between IL-10 and IL-12, we explored whether IgA could regulate this other immunoregulatory cytokine. In human monocytes and monocyte-derived dendritic cells preincubated with IFN- before stimulation by LPS, suppression of p40 and IL-12p70 production was observed upon IgA treatment during IFN- priming. Washout experiments and inhibition of IFN--induced CXCL10 (IP-10) and FcRI (CD64) indicated that inhibition by IgA occurred at both the LPS and IFN- levels. Inhibition was not affected by blockade of IL-10 or MAPK but involved FcRI/CD89-mediated suppression of STAT1 phosphorylation. These data indicate that FcRI ligation on human monocytes and dendritic cells inhibits IL-12 expression and type 1 activation by interfering with STAT1 activation.


PubMed | Institute Of Recherche Experimentale Et Clinique
Type: Journal Article | Journal: Current diabetes reports | Year: 2013

Cell therapy is currently considered as a potential therapeutic alternative to traditional treatments of diabetes. Islet and whole pancreas transplantations provided the proof-of-concept of glucose homeostasis restoration after replenishment of the deficiency of cells responsible for the disease. Current limitations of these procedures have led to the search for strategies targeting replication of pre-existing cells or transdifferentiation of progenitors and adult cells. These investigations revealed an unexpected plasticity towards cells of adult cells residing in pancreatic epithelium (eg, acinar, duct, and cells). Here we discuss recent developments in -cell replication and -cell transdifferentiation of adult epithelial pancreatic cells, with an emphasis on techniques with a potential for clinical translation.


PubMed | Institute Of Recherche Experimentale Et Clinique
Type: Journal Article | Journal: Journal of endocrinological investigation | Year: 2013

PTH is related to left ventricular hypertrophy and its circulating levels are associated with worse prognosis in patients with heart failure (HF). The objectives of our study were to measure the circulating levels of bioactive PTH 1-84 through third-generation assay in HF patients, to determine their association with the disease severity as well as their relation with recognized biomarkers of HF worsening and prognosis.PTH 1-84 concentrations were determined in 76 HF patients and in 49 healthy volunteers. Circulating levels of amino-terminal proatrial natriuretic peptide (Nt-proANP), B-type natriuretic peptide (BNP), Nt-proBNP, proBNP, and big endothelin-1 (Big ET-1) were also measured.HF patients had in- creased PTH 1-84 levels in comparison to controls. A significant increase of the PTH 1-84 circulating concentrations was observed according to the New York Heart Association functional classes. PTH 1-84 circulating concentrations were also significantly correlated with Nt-proANP, BNP, Nt-proBNP, proBNP, and Big ET-1.PTH 1-84 circulating levels are significantly increased in HF patients in comparison to healthy individuals. Our study has also demonstrated that circulating concentrations of bioactive PTH are related to HF severity and well-established biomarkers of the worsening of the disease.


Dolmans M.-M.,Institute Of Recherche Experimentale Et Clinique | Marinescu C.,Institute Of Recherche Experimentale Et Clinique | Saussoy P.,Catholic University of Louvain | Van Langendonckt A.,Institute Of Recherche Experimentale Et Clinique | And 2 more authors.
Blood | Year: 2010

Ovarian tissue cryopreservation is currently proposed to young cancer patients to preserve their fertility before radiochemotherapy. The potential risk is that the tissue might harbor malignant cells that could induce disease recurrence. We therefore decided to evaluate the presence of leukemic cells in cryopreserved ovarian tissue from 18 leukemic patients: 6 with chronic myeloid leukemia (CML) and 12 with acute lymphoblastic leukemia (ALL). In each case, histology, quantitative reverse-transcribed polymerase chain reaction (RT-PCR) and long-term (6 months) xenografting to immunodeficient mice were used. Histology did not identify any malignant cells in the ovarian tissue. By quantitative RT-PCR, 2 of 6 CML patients were positive for BCR-ABL in their ovarian tissue. Among the 12 ALL patients, 7 of the 10 with available molecular markers showed positive leukemic markers in their ovarian tissue (translocations or rearrangement genes). Four mice grafted with ovarian tissue from ALL patients developed intraperitoneal leukemic masses. In conclusion, this study demonstrates, by quantitative RT-PCR, ovarian contamination by malignant cells in acute as well as chronic leukemia, whereas histology fails to do so. Moreover, chemotherapy before ovarian cryopreservation does not exclude malignant contamination. Finally, reimplantation of cryopreserved ovarian tissue from ALL and CML patients puts them at risk of disease recurrence. © 2010 by The American Society of Hematology.


Marique L.,Institute Of Recherche Experimentale Et Clinique | Van Regemorter V.,Institute Of Recherche Experimentale Et Clinique | Gerard A.-C.,Institute Of Recherche Experimentale Et Clinique | Craps J.,Institute Of Recherche Experimentale Et Clinique | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are thyroid autoimmune disorders driven by Th1 and Th2 immune responses, respectively. Caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX) are thought to be part of the thyroxisome, which is essential to maintain thyroid hormone synthesis, at the apical membrane. Objectives: To analyze the thyroxisome in HT and GD thyroids, we investigated Cav-1, DUOX, and TPO expression as well as markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant defenses. The effects of cytokines on Cav-1 expression were analyzed in vitro. Results: In HT, the decrease in Cav-1, DUOX, and TPO expression was marked in follicles having the morphological aspect of active follicles in normal glands and thus called active-like follicles. T 4 was not detected in the colloid but in the cytoplasm as well asDUOXand TPO. These abnormalities were associated with increased OS and cell damage. In the hypofunctioning follicles of HT and normal thyroids, Cav-1, DUOX, and TPO were not expressed. In GD, they were expressed at the apical pole of thyrocytes, and T4 accumulated in the colloid of all follicles. Th1 cytokines IL-1α/interferon decreased Cav-1 expression in vitro, whereas the Th2 cytokine IL-4 had no effect. Conclusion: Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis. © 2014 by the Endocrine Society.

Loading Institute Of Recherche Experimentale Et Clinique collaborators
Loading Institute Of Recherche Experimentale Et Clinique collaborators