Papers by Assia Eljaafari
Diabetologia, 2009
Aims/hypothesis Displaying immunomodulatory capacities, mesenchymal stem cells (MSCs) are conside... more Aims/hypothesis Displaying immunomodulatory capacities, mesenchymal stem cells (MSCs) are considered as beneficial agents for autoimmune diseases. The aim of this study was to examine the ability of MSCs to prevent autoimmune diabetes in the NOD mouse model. Methods Prevention of spontaneous insulitis or of diabetes was evaluated after a single i.v. injection of MSCs in 4-week-old female NOD mice, or following the coinjection of MSCs and diabetogenic T cells in irradiated male NOD recipients, respectively. The frequency of CD4 + FOXP3 + cells and Foxp3 mRNA levels in the spleen of male NOD recipients were also quantified. In vivo cell homing was assessed by monitoring 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled T cells or MSCs. In vitro, cell proliferation and cytokine production were assessed by adding graded doses of irradiated MSCs to insulin B9-23 peptide-specific T cell lines in the presence of irradiated splenocytes pulsed with the peptide. Results MSCs reduced the capacity of diabetogenic T cells to infiltrate pancreatic islets and to transfer diabetes. This protective effect was not associated with the modification of diabetogenic T cell homing, but correlated with a preferential migration of MSCs to pancreatic lymph nodes. While injection of diabetogenic T cells resulted in a decrease in levels of FOXP3 + regulatory T cells, this decrease was inhibited by MSC co-transfer. Moreover, MSCs were able to suppress both allogeneic and insulin-specific proliferative responses in vitro. This suppressive effect was associated with the induction of IL10-secreting FOXP3 + T cells. Conclusions/interpretation MSCs prevent autoimmune beta cell destruction and subsequent diabetes by inducing regulatory T cells. MSCs may thus offer a novel cell-based approach for the prevention of autoimmune diabetes and for islet cell transplantation.
Human mesenchymal stem cells suppress induction of cytotoxic response to alloantigens
Biorheology, 2004
Mesenchymal stem cells (MSC) fail to induce allogeneic responses in mixed lymphocyte reaction ass... more Mesenchymal stem cells (MSC) fail to induce allogeneic responses in mixed lymphocyte reaction assays. Because MSC express HLA class I molecules, here we investigated whether they could be recognized as allogeneic targets by cytolytic T lymphocytes (CTL). With this aim, CTL precursor (CTLp) frequencies were measured following stimulation of T cells with either allogeneic mononuclear cells (MNC) or MSC originated from the same human bone marrow donor. Lysis of MSC was measured at day 10 of culture in standard chromium release assays. In addition, allogeneic PHA blast T cells or B-EBV lymphoblastoid cell lines (LCLs) generated from the same donor were used as positive controls of lysis. Our results showed that when allogeneic MNC were used to stimulate T cells, a high CTLp frequency was detected towards MSC targets. However, when MSC were used as stimulators, CTLp frequencies were markedly altered whatever the targets used, i.e.: MSC, PHA blast T cells or EBV-B LCLs. Moreover, when gra...
Allogreffe de mains: expérience lyonnaise
Annales de Chirurgie Plastique Esthétique, 2007
Hand allograft is a method in the stage of clinical experimentation, which is reserved in France ... more Hand allograft is a method in the stage of clinical experimentation, which is reserved in France for the treatment of bilateral traumatic amputees. This study reports the Lyon team experience, which is pioneer in this domain. Four patients (3 males and 1 female) underwent seven (one unilateral and three bilateral) hand transplantations from September 1998 to February 2007. The level
Introduction As opposed with lean adipose tissues (AT), obese AT are heavily infiltrated with var... more Introduction As opposed with lean adipose tissues (AT), obese AT are heavily infiltrated with variety of inflammatory cells. Among them, Th17 cells are found not only within AT, but also in the periphery in obese subjects. We have demonstrated that AT-derived stem cells (ASC), or their progenitors, contribute to inflammation through promotion of Th-17 cells, provided that they are issued from obese-, but not lean-AT (Diabetes, 2015; Adipocyte, 2016). Because obesity is associated with increased prevalence of various cancers, including hepatic or breast cancer, we postulated herein that ASC-mediated promotion of Th17 cells might result in tumorogenesis progression. Materials and Methods: Human ASC were isolated from WAT of obese donors (obASC). Mononuclear cells (MNC) were collected from blood donors. PHA-activated co-cultures of obASC/MNC, which increase secretion of IL-17A, IL-1b and IL-6, were performed. Conditioned media (CM) were collected from such cultures, and added to HuH7 (...
Contribution of obese adipose tissue-derived stem cells to hepato-or breast-carcinoma inflammation, through promotion of Th17 cells and activation of IL-1b by monocytes
Background and aims:As opposed with lean adipose tissues (AT), obese AT are heavily infiltrated w... more Background and aims:As opposed with lean adipose tissues (AT), obese AT are heavily infiltrated with variety of inflammatory cells such as macrophages and Th17 cells. Obesity-mediated chronic low-grade inflammation is known to contribute to tumor progression in various cancers, including hepatic and breast cancers. Because we have previous-ly demonstrated, using co-culture experiments, that obese AT-derived stem cells (obASC) contribute to AT inflammation through promotion of Th17 cells, and activation of IL-1β-secreting monocytes, we postulated herein that such inflammatory environment could contribute to tumor progression in cancer-suffering obese patients.Materials and methods:Human ASC were isolated from AT of obese donors. Mononuclear cells (MNC) were collected from healthy blood donors. Co-cultures of obASC and MNC were activated for 48 hours with phytohemagglutinin A ( PHA), a T cell mitogen, or not. Conditionned media (CM) were collected, and added for 24h to cultures of HuH...
Http Www Theses Fr, Dec 17, 2007
Immune homeostasis is important for the protection of a host from pathogen aggression, as well as... more Immune homeostasis is important for the protection of a host from pathogen aggression, as well as for preventing autoimmunity. Dendritic cells (DCs), the most potent antigen presenting cells, are critical in innate, adaptive immunity and in central tolerance. Recently, their involvement in peripheral tolerance has been shown. Whether DCs induce immunity or tolerance depends on their state of maturation. Different subsets of tolerogenic DCs have been identified in vivo, either in physiological, or pathological conditions, such as tumors, or GVHD. Moreover, tolerogenic DCs can be generated in vitro, by using different culture conditions, such as IL-10 or TGF-β. In our study, we obtained tolerogenic DCs, by culturing them in the presence of human mesenchymal stem cells (MSCs).
Les acides gras poly-insaturés de type oméga 3 inhibent la production d’IL-17A médiée par les cellules souches du tissu adipeux, en diminuant l’expression d’ICAM-1, chez le sujet obèse
Nutrition Clinique et Métabolisme
Endocrinology&Metabolism International Journal
Obesity, a worldwide public health problem is often associated with the metabolic syndrome. Indee... more Obesity, a worldwide public health problem is often associated with the metabolic syndrome. Indeed, infiltration of immune cells within obese adipose tissues participates to the establishment of a chronic sub-inflammatory environment leading to insulin resistance. As in various inflammatory disorders, fasting regimens have demonstrated their beneficial effects in reducing obesity and its subsequent metabolic syndrome, through reduction of inflammation in white adipose tissues. In this review, we will highlight how caloric restriction can be protective against obesity associated inflammation and metabolic syndrome. Background: Obesity is dependent on genetic factors, lifestyle, and diet. Increased incidence of obesity and its subsequent complications, such as type 2 diabetes (T2D), are a worldwide public health problem, as one third of the population in some developed countries is obese, i.e: having a body mass index (BMI) more than 30 kg/m 2. Interconnection of obesity with metabolic alterations or diseases, such as T2D, dyslipidemia, hypertension, and atherosclerosis is widely recognized, as the metabolic syndrome. 1 Moreover, obesity is also known to be a risk factor of systemic or organ inflammation.
Evaluation of human MSCs cell cycle, viability and differentiation in micromass culture
Biorheology, 2006
Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct mesenchymal tissu... more Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct mesenchymal tissue cells. They are easy to expand while maintaining their undifferentiated state, which suggests that these cells could be an attractive cell source for tissue engineering of cartilage. In vitro high density micromass culture has been widely used for chondrogenesis induction. Our objective was to investigate human MSCs cell cycle, viability and differentiation in these conditions. Therefore, to induce human MSCs chondrogenesis, micromasses were cultured in the presence of transforming growth factor-beta1 in serum free medium for 21 days. Cell cycle, cell viability and cell phenotype were analyzed by flow cytometry. From day 0 to 7, the G0/G1 phase increased, whereas the S phase decreased gradually, but cell cycle phases (S, G0/G1 and G2/M) did not significantly change after day 7. Less than 10% of cells were apoptotic, but no necrosis was observed, even at day 21. We observed a decrease i...
American Journal of Hematology
Mechanisms Involved in the Induction of Tolerance in Allogeneic Hand Transplantation: A Proposal
Hand Transplantation, 2007
The first human unilateral hand allotransplantation was performed in Lyon, in September 1998, fol... more The first human unilateral hand allotransplantation was performed in Lyon, in September 1998, followed by other cases all over the world. The technical feasibility of this procedure has thus been demonstrated. Whereas antigenicity of the skin was considered as the major obstacle to human composite tissue allotransplantation, clinical outcomes have demonstrated that hand allotransplantation seems to be well tolerated without drastic immunosuppressive drugs. This chapter briefly describes current advances in the field of tolerance to organ transplantation and elaborates suggestions for the reasons why hand transplantations are likely to be immunologically well tolerated by the host.
Immunomonitoring of Face and Hand Grafted Patients by Comparing Mrna Markers in Tissues Versus Blood Can Help to Differentiate Rejection Versus Viral Infection Episodes
Transplantation Journal, 2010
Transfusion Clinique Et Biologique, 1998
Diabetes & Metabolism, 2014
O55 Un modèle préclinique de diabète de type I chez une souris humanisée exprimant les gènes HLA ... more O55 Un modèle préclinique de diabète de type I chez une souris humanisée exprimant les gènes HLA de classe I et II et de l'insuline humaine
Cells
The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfu... more The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly different...
Involvement of glycated albumin in adipose-derived-stem cell-mediated interleukin 17 secreting T helper cell activation
World Journal of Stem Cells
IL-17A contributes to propagation of inflammation but does not impair adipogenesis and/or insulin response, in adipose tissue of obese individuals
Cytokine
Omega-3 Polyunsaturated Fatty Acids Inhibit IL-17A Secretion through Decreased ICAM-1 Expression in T Cells Co-Cultured with Adipose-Derived Stem Cells Harvested from Adipose Tissues of Obese Subjects
Molecular Nutrition & Food Research
Journal of Clinical Medicine
Obesity is associated with low-grade chronic inflammation. Indeed, adipose tissues (AT) in obese ... more Obesity is associated with low-grade chronic inflammation. Indeed, adipose tissues (AT) in obese individuals are the former site of progressive infiltration by pro-inflammatory immune cells, which together with increased inflammatory adipokine secretion induce adipocyte insulin resistance. IL-17-producing T (Th17) cells are part of obese AT infiltrating cells, and are likely to be promoted by adipose tissue-derived mesenchymal stem cells, as previously reported by our team. Whereas Th17 cell are physiologically implicated in the neutralization of fungal and bacterial pathogens through activation of neutrophils, they may also play a pivotal role in the onset and/or progression of chronic inflammatory diseases, or cancer, in which obesity is recognized as a risk factor. In this review, we will highlight the pathogenic role of IL-17A producing cells in the mechanisms leading to inflammation in obesity and to progression of obesity-related inflammatory diseases.
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Papers by Assia Eljaafari