Publications of Céline GREGOIRE
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See detailIn Vitro Th17-Polarized Human CD4(+) T Cells Exacerbate Xenogeneic Graft-versus-Host Disease.
Delens, Loïc ULiege; Ehx, Gregory ULiege; SOMJA, Joan ULiege et al

in Biology of Blood and Marrow Transplantation (2019), 25

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. The role of Th17 cells in its pathophysiology remains a matter of debate. In this ... [more ▼]

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. The role of Th17 cells in its pathophysiology remains a matter of debate. In this study, we assessed whether enrichment of human peripheral blood mononuclear cells (PBMCs) with in vitro Th17-polarized CD4(+) T cells would exacerbate xenogeneic GVHD (xGVHD) into NOD-scid IL-2Rgamma null (NSG) mice. Naive human CD4(+) T cells were stimulated under Th17-skewing conditions for 8 to 10 days and then coinjected in NSG mice with fresh PBMCs from the same donor. We observed that Th17-polarized cells engrafted and migrated toward xGVHD target organs. They also acquired a double-expressing IL-17A(+)IFNgamma(+) profile in vivo. Importantly, cotransfer of Th17-polarized cells (1x10(6)) with PBMCs (1x10(6)) exacerbated xGVHD compared with transplantation of PBMCs alone (2x10(6)). Furthermore, PBMC cotransfer with Th17-polarized cells was more potent for xGVHD induction than cotransfer with naive CD4(+) T cells stimulated in nonpolarizing conditions (Th0 cells, 1x10(6)+1x10(6) PBMCs) or with Th1-polarized cells (1x10(6)+1x10(6) PBMCs). In summary, our results suggest that human Th17-polarized cells can cooperate with PBMCs and be pathogenic in the NSG xGVHD model. [less ▲]

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See detailComparison of Mesenchymal Stromal Cells From Different Origins for the Treatment of Graft-vs.-Host-Disease in a Humanized Mouse Model.
Grégoire, Céline ULiege; Ritacco, Caroline ULiege; Hannon, Muriel ULiege et al

in Frontiers in Immunology (2019), 10

Mesenchymal stromal cells (MSCs) have potent immunomodulatory properties that make them an attractive tool against graft- vs.-host disease (GVHD). However, despite promising results in phase I/II studies ... [more ▼]

Mesenchymal stromal cells (MSCs) have potent immunomodulatory properties that make them an attractive tool against graft- vs.-host disease (GVHD). However, despite promising results in phase I/II studies, bone marrow (BM-) derived MSCs failed to demonstrate their superiority over placebo in the sole phase III trial reported thus far. MSCs from different tissue origins display different characteristics, but their therapeutic benefits have never been directly compared in GVHD. Here, we compared the impact of BM-, umbilical cord (UC-), and adipose-tissue (AT-) derived MSCs on T-cell function in vitro and assessed their efficacy for the treatment of GVHD induced by injection of human peripheral blood mononuclear cells in NOD-scid IL-2Rgamma(null) HLA-A2/HHD mice. In vitro, resting BM- and AT-MSCs were more potent than UC-MSCs to inhibit lymphocyte proliferation, whereas UC- and AT-MSCs induced a higher regulatory T-cell (CD4(+)CD25(+)FoxP3(+))/T helper 17 ratio. Interestingly, AT-MSCs and UC-MSCs activated the coagulation pathway at a higher level than BM-MSCs. In vivo, AT-MSC infusions were complicated by sudden death in 4 of 16 animals, precluding an analysis of their efficacy. Intravenous MSC infusions (UC- or BM- combined) failed to significantly increase overall survival (OS) in an analysis combining data from 80 mice (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.32-1.08, P = 0.087). In a sensitivity analysis we also compared OS in control vs. each MSC group separately. The results for the BM-MSC vs. control comparison was HR = 0.63 (95% CI 0.30-1.34, P = 0.24) while the figures for the UC-MSC vs. control comparison was HR = 0.56 (95% CI 0.28-1.10, P = 0.09). Altogether, these results suggest that MSCs from various origins have different effects on immune cells in vitro and in vivo. However, none significantly prevented death from GVHD. Finally, our data suggest that the safety profile of AT-MSC and UC-MSC need to be closely monitored given their pro-coagulant activities in vitro. [less ▲]

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See detailReview article: mesenchymal stromal cell therapy for inflammatory bowel diseases
GREGOIRE, Céline ULiege; LECHANTEUR, Chantal ULiege; BRIQUET, Alexandra ULiege et al

in Alimentary Pharmacology and Therapeutics (2017), 45

Background Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells ... [more ▼]

Background Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair. Aim To review the current data on mesenchymal stromal cell therapy in IBD. Method We searched PubMed and ‘ClinicalTrials.gov’ databases using the terms ‘mesenchymal stromal cells’, ‘mesenchymal stem cell transplantation’, ‘inflammatory bowel diseases’, ‘Crohn disease’ and ‘colitis, ulcerative’. Additional publications were identified from individual article reference lists. Results MSCs include inhibition of Th1/Th17 lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen-presenting cells into a regulatorylike profile, and stimulation of epithelial cell differentiation and proliferation. More than 200 patients with refractory fistulas have been treated with local injections of MSCs, resulting in complete response in more than half, and in overall response in approximately two thirds of patients. In refractory luminal Crohn’s disease, 49 cases of systemic MSC infusions have been reported, while trials with autologous MSCs resulted in mitigated responses, studies using allogeneic MSCs were promising, with around 60% of patients experiencing a response and around 40% achieving clinical remission. Conclusions Mesenchymal stromal cells might represent a promising therapy for IBD, especially for Crohn’s disease. There remain many unsolved questions concerning the optimal origin and source of mesenchymal stromal cells, dosage and modalities of administration. Moreover, mesenchymal stromal cells still need to prove their effectiveness compared with conventional treatments in randomised controlled trials. [less ▲]

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See detailThe use of mesenchymal stromal cells in solid organ transplantation
GREGOIRE, Céline ULiege; DETRY, Olivier ULiege; Jouret, François ULiege et al

in The Biology and Therapeutic Application of Mesenchymal Cells (2017)

Organ transplantation is the only definitive treatment for many critical diseases of the liver, kidney, heart, pancreas, and lungs. Although it is the primary therapeutic option at present, transplanted ... [more ▼]

Organ transplantation is the only definitive treatment for many critical diseases of the liver, kidney, heart, pancreas, and lungs. Although it is the primary therapeutic option at present, transplanted patients have to deal with the numerous side effects of life-long dependence on immunosuppressive drugs, and these drugs still fail to prevent chronic rejection of the transplanted organ in many cases. The risk of developing cancer and opportunistic infections is also markedly increased in solid organ transplant (SOT) recipients receiving long-term immunosuppressive therapy. Cancer and opportunistic infections cannot be completely avoided since they result from the immunosuppressive drugs used posttransplant that affect not only the anti-graft response but also the entire immune response. Finding a way to establish donor-specific immunological tolerance without the need for nonspecific immunosuppression remains one of the major goals in transplantation medicine [1,2]. Another important aim is the improvement of graft survival and function. Overall, graft survival is about 15 years, but the increasing shortage of organs has led to the use of expanded criteria for donor organs often donated by older individuals, which are less robust organs than those donated by younger donors. Mesenchymal stromal cell (MSCs) are currently being evaluated in SOT with the hope of achieving more selective immunosuppression, better graft function, and longer graft survival. [less ▲]

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See detailThe role of mesenchymal stromal cells in the treatment of ulcerative colitis and Crohn’s disease
GREGOIRE, Céline ULiege; Louis, Edouard ULiege; BRIQUET, Alexandra ULiege et al

in The Biology and Therapeutic Application of Mesenchymal Cells (2017)

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See detailYellow nail syndrome after allogeneic haematopoietic stem cell transplantation in two patients with multiple myeloma
Grégoire, Céline ULiege; GUIOT, Julien ULiege; Vertenoeil, Gaëlle ULiege et al

in Acta Clinica Belgica (2016), 71

Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have ... [more ▼]

Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have been reported, but a lot of patients probably elude proper diagnosis because of both variability of symptoms and ignorance of this syndrome by many physicians. The pathogenesis remains unclear, and could involve functional lymphatic abnormalities, microvasculopathy or lymphocyte deficiency, but none of these hypotheses seems fully satisfactory. Clinical Presentation: We report for the first time two cases of YNS associated with multiple myeloma relapsing after non-myeloablative haematopoietic cell transplantation (HCT). In these two cases, onset or worsening of YNS symptoms followed graft-versus-host disease (GvHD) manifestations. Intervention: Corticosteroids given to treat GvHD also improved YNS manifestations. Conclusion: YNS after HCT might be a microvascular manifestation of endothelial GvHD and corticosteroids might be an effective treatment. [less ▲]

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See detailMultipotent mesenchymal stromal cell therapy for steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation
SERVAIS, Sophie ULiege; GREGOIRE, Céline ULiege; BARON, Frédéric ULiege et al

in Belgian Journal of Hematology (2016), 7

Steroid-refractory acute graft-versus-host disease is a severe complication after allogeneic stem cell transplantation. So far, its treatment remains very challenging since the current therapies do not ... [more ▼]

Steroid-refractory acute graft-versus-host disease is a severe complication after allogeneic stem cell transplantation. So far, its treatment remains very challenging since the current therapies do not offer significant benefits. Among the most recent approaches, multipotent mesenchymal stromal cell-based therapy has attracted great interest over the past decade. Here, we briefly reviewed the current knowledges about the immunomodulatory properties of multipotent mesenchymal stromal cells as well as results of preclinical and clinical studies having assessed their efficacy to modulate steroid-refractory acute graft-versus-host disease. [less ▲]

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See detailMesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.
Rowart, Pascal ULiege; ERPICUM, Pauline ULiege; Detry, Olivier ULiege et al

in Journal of Immunology Research (2015), 602597

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and ... [more ▼]

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT. [less ▲]

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See detailCellules stromales mésenchymateuses et transplantation d'organes
DETRY, Olivier ULiege; JOURET, François ULiege; VANDERMEULEN, Morgan ULiege et al

in Revue Médicale de Liège (2014), 69

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of ischemic injury, and ... [more ▼]

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of ischemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation. [less ▲]

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See detailRationale for the potential use of mesenchymal stromal cells in liver transplantation.
VANDERMEULEN, Morgan ULiege; GREGOIRE, Céline ULiege; BRIQUET, Alexandra ULiege et al

in World Journal of Gastroenterology (2014), 20(44), 16418-32

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing cells that reside essentially in the bone marrow as a non-hematopoietic cell population, but may also be isolated from the connective ... [more ▼]

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing cells that reside essentially in the bone marrow as a non-hematopoietic cell population, but may also be isolated from the connective tissues of most organs. MSCs represent a heterogeneous population of adult, fibroblast-like cells characterized by their ability to differentiate into tissues of mesodermal lineages including adipocytes, chondrocytes and osteocytes. For several years now, MSCs have been evaluated for their in vivo and in vitro immunomodulatory and 'tissue reconstruction' properties, which could make them interesting in various clinical settings, and particularly in organ transplantation. This paper aims to review current knowledge on the properties of MSCs and their use in pre-clinical and clinical studies in solid organ transplantation, and particularly in the field of liver transplantation. The first available clinical data seem to show that MSCs are safe to use, at least in the medium-term, but more time is needed to evaluate the potential adverse effects of long-term use. Many issues must be resolved on the correct use of MSCs. Intensive in vitro and pre-clinical research are the keys to a better understanding of the way that MSCs act, and to eventually lead to clinical success. [less ▲]

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