Publications of Céline GREGOIRE
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See detailHigh proportion of terminally-differentiated regulatory T cells after allogeneic hematopoietic stem cell transplantation
Ritacco, Caroline ULiege; Ehx, Grégory ULiege; GREGOIRE, Céline ULiege et al

in Bone Marrow Transplantation (in press)

It is now well-established that regulatory T cells (Treg) represent a heterogeneous group of CD4+ T cells. Previous studies have demonstrated that Treg homeostasis was impacted by allogeneic hematopoietic ... [more ▼]

It is now well-established that regulatory T cells (Treg) represent a heterogeneous group of CD4+ T cells. Previous studies have demonstrated that Treg homeostasis was impacted by allogeneic hematopoietic cell transplantation (allo-HCT) and particularly so in patients with chronic graft-versus-host disease (GVHD). Here, we first assessed the ability of various Treg subsets to phosphorylate STAT5 in response to IL-2 or IL-7 stimulation in vitro. We then compared the frequencies of different Treg subtypes in healthy controls as well as in allo-HCT patients with or without chronic GVHD. The highest phosphorylated STAT5 (pSTAT5) signal in response to IL-2 was observed in the CD45RO+CD26−CD39+HLA-DR+ Treg fraction. In contrast, naive Treg were mostly less susceptible to IL-2 stimulation in vitro. Following IL-7 stimulation, most Treg subpopulations upregulated pSTAT5 expression but to a lesser extent than conventional T cells. Compared to healthy controls, allo-HCT patients had lower frequencies of the naive CD45RAbrightCD26+ Treg subpopulation but higher frequencies of the most differentiated memory CD45RO+CD26−CD39+ Treg subpopulations. Further, unbiased analysis revealed that six Treg clusters characterized by high expression of CD25, HLA-DR, and ICOS were significantly more frequent in patients with no or with limited chronic GVHD than in those with moderate/severe chronic GVHD. [less ▲]

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See detailMesenchymal stromal cell-based immunomodulation in graft-versus-host disease and Crohn's disease
GREGOIRE, Céline ULiege

Doctoral thesis (2020)

Mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue repair properties that make them an attractive tool against graft-vs-host disease (GVHD) and Crohn’s disease. Despite promising ... [more ▼]

Mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue repair properties that make them an attractive tool against graft-vs-host disease (GVHD) and Crohn’s disease. Despite promising results in phase I/II studies, bone marrow (BM-) derived MSCs have failed to demonstrate their superiority over placebo in two phase III trials. MSCs from different tissue origins display different characteristics, but their therapeutic benefits have never been directly compared in GVHD. In the first part of this work, 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-2R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. The safety of MSC therapy in Crohn’s disease has been showed in several studies, but its efficacy and mechanisms of action still need to be investigated. In the second part of this work, we aimed to further assess the safety and efficacy of intravenous injections of allogeneic bone marrow MSCs in Crohn’s disease and to improve the comprehension of their mechanisms of action in order to better design the next phase III trials. Thirteen patients with active refractory Crohn’s disease were enrolled to receive 2 injections of 1.5-2.0x106 MSCs/kg body weight at week 0 and 4. Primary endpoints were safety and clinical response defined by a 100-point decrease in Crohn’s Disease Activity Index (CDAI) at week 8. Secondary endpoints were clinical response, remission (CDAI<150), CDAI, C-reactive protein (CRP) and faecal calprotectin levels at weeks 2, 4, 8 and 12, and incidence of infections by week 12. Ancillary studies included evaluation of immune modulation. At week 8, 2/13 patients achieved clinical response, and CDAI was decreased in 8/10 evaluable patients (mean CDAI decrease of 31.2±80.6). MSC infusions were well tolerated and safe. There were no statistically significant differences between CDAI, CRP levels and faecal calprotectin levels at each time points. We observed a significant increase in the proportions of natural killer (NK) and NKT cells between week 0 and 12. In conclusion, our study provides supplementary data on the safety of systemic infusion of MSCs in luminal Crohn’s disease and guides the following research towards the study of the interactions between NK cells and MSCs. [less ▲]

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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 detailInfusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study.
ERPICUM, Pauline ULiege; WEEKERS, Laurent ULiege; DETRY, Olivier ULiege et al

in Kidney International (2019), 95

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year ... [more ▼]

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs ( approximately 2 x 10(6)/kg) on day 3 +/- 2 post-transplant and were compared to 10 concurrent controls. No adverse effects were noted at MSC injection. One participant with a history of cardiac disease had a non-ST-elevation myocardial infarction approximately 3 hours after MSC infusion. Incidences of opportunistic infections and acute rejection were similar. At day 7 post-transplant, estimated glomerular filtration rate (eGFR) in MSC-treated recipients reached 48.6 ml/min/1.73m(2), compared to 32.5 ml/min/1.73m(2)in controls and 29.3 ml/min/1.73m(2)in our overall cohort of kidney transplant recipients. No difference in eGFR was found at 1 year. MSC-treated recipients showed increased frequencies of regulatory T cells at day 30, with no significant change in B cell frequencies compared to concurrent controls. Four MSC-treated participants developed antibodies against MSC or shared kidney-MSC HLA, with only 1 with MFI >1500. A single infusion of third-party MSC following kidney transplantation appears to be safe, with one cardiac event of unclear relationship to the intervention. MSC therapy is associated with increased regulatory T cell proportion and with improved early allograft function. Long-term effects, including potential immunization against MSC, remain to be studied. [less ▲]

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See detailAllogeneic mesenchymal stromal cells for refractory luminal Crohn's disease: A phase I-II study.
GREGOIRE, Céline ULiege; BRIQUET, Alexandra ULiege; PIRENNE, Caroline et al

in Digestive and Liver Disease (2018), 50(11), 1251-1255

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See detailNouveautes dans la prise en charge du myelome.
Vrancken, Louise; Muller, Joséphine ULiege; Lejeune, Margaux ULiege et al

in Revue Médicale Suisse (2018), 14(615), 1438-1442

Multiple myeloma is the second most frequent hematological malignancy. Unfortunately, it is still incurable. A better understanding of the myeloma pathophysiology favored the development of new ... [more ▼]

Multiple myeloma is the second most frequent hematological malignancy. Unfortunately, it is still incurable. A better understanding of the myeloma pathophysiology favored the development of new therapeutic molecules that improved both survival and quality of life of patients. Diagnostic and prognostic criteria for myeloma have been reviewed and help to detect multiple myeloma more early and further help to define the best therapeutic strategy. These new regimens are associated with side effects that differ from those of classic molecules and that we have to be able to recognize and to treat appropriately. [less ▲]

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See detailTh17 cells impact on xenogeneic graft-versus-host disease
Delens, Loïc ULiege; SERVAIS, Sophie ULiege; Ehx, Grégory ULiege et al

Poster (2017, May 24)

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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 detailImpact des cellules Th17 sur la GVH xénogénique
Delens, Loïc ULiege; SERVAIS, Sophie ULiege; Ehx, Grégory ULiege et al

Conference (2016, November 18)

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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 detailLa prothèse valvulaire idéale n’existe toujours pas. Quels facteurs entrent en compte pour orienter les choix d’une valve mécanique ou biologique ?
GREGOIRE, Céline ULiege; Nellessen, Eric; Defraigne, Jean-Olivier ULiege et al

in Revue Médicale de Liège (2014), 69(11), 600-604

The prevalence of valvular heart diseases reaches 2.5% in the overall population. Aortic valve replacement is one of the most common surgical procedures. We report the story of a female patient whose ... [more ▼]

The prevalence of valvular heart diseases reaches 2.5% in the overall population. Aortic valve replacement is one of the most common surgical procedures. We report the story of a female patient whose aortic mechanical valve, implanted at the age of 54 years at the time of a mitral valve repair surgery, had to be replaced 14 years later, due to the development of a subvalvular pannus narrowing the valvular orifice. We use this clinical story to compare the advantages and disadvantages of repair surgery and valve replacement with a biological or mechanical prosthesis, and summarize the latest evidence for the choice of the most adequate prosthesis for a particular patient’s profile. [less ▲]

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See detailHuman bone marrow, umbilical cord or liver mesenchymal stromal cells fail to improve liver function in a model of CCl4-induced liver damage in NOD/SCID/IL-2Ry(null) mice
BRIQUET, Alexandra ULiege; GREGOIRE, Céline ULiege; Comblain, Fanny ULiege et al

in Cytotherapy (2014), 16

Background aims. Transplantation is the gold standard procedure for treating acute and chronic end-stage liver diseases. Given the shortage of organs, the development of cellular sources other than human ... [more ▼]

Background aims. Transplantation is the gold standard procedure for treating acute and chronic end-stage liver diseases. Given the shortage of organs, the development of cellular sources other than human liver is urgent. The main objective of this project was to examine the effect of mesenchymal stromal cell (MSC) (bone marrow, umbilical cord and liver MSCs) intravenous injection on liver regeneration in a model of hepatic damage in NOD/SCID/IL non-obese diabetic/severe combined immunodeficient/Interleukin-2Rg(null) (NSG) mice. Methods. Mice received 3 intraperitoneal injections of CCl4 Carbon tetrachloride per week for 4 weeks. Forty-eight hours after the last injection of CCl4, mice received 500,000 MSCs or phosphate-buffered saline by intravenous injection. We examined hepatic damage by means of quantitative image analysis and blood enzyme analysis 24 h, 1 week or 8 weeks after MSC or phosphate-buffered saline injection. We also examined MSC homing by means of real-time polymerase chain reaction of human albumin. Results. We adapted a model of liver injury in immunodeficient mice. In this model, accumulation of collagen in newly formed scar septa was apparent up to 8 weeks after CCl4 treatment. Human albumin DNA was found in all organs tested. However, intravenous MSC injection, even after CXCR4 C-X-C chemokine receptor type 4 transduction and whatever the origin of MSCs, failed to improve liver damage. Conclusions. In this liver injury model, MSCs were propagated in various tissues, particularly filtering organs. For the treatment of hepatic damage, intravenous administration of moderate doses of MSCs does not appear to be effective. Yet, this adapted liver injury model is appropriate for investigating engraftment of human cells. [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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