References of "Giet, Olivier"
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See detailUNE INJECTION UNIQUE DE CELLULES STROMALES MESENCHYMATEUSES AU JOUR 3 APRES GREFFE HEPATIQUE EST INSUFFISANTE POUR INDUIRE UNE TOLERANCE OPERATIONNELLE
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

in Transplant International (2017, January), 30(suppl 1), 812

Introduction: Mesenchymal stromal cell (MSC) infusion could be a mean to establish donor-specific immunological tolerance in solid organ recipients. The aim of this phase 2 study was test the hypothesis ... [more ▼]

Introduction: Mesenchymal stromal cell (MSC) infusion could be a mean to establish donor-specific immunological tolerance in solid organ recipients. The aim of this phase 2 study was test the hypothesis of possible induction of operative tolerance by third-party MSC in liver transplant (LT) recipients. Methods: 10 stable and low-risk LT recipients under standard immunosup- pression (Tac-MMF- low dose steroids) received 1.5–3 9 106/kg third-party MSCs on post-operative day 3 ` 2. By protocol, progressive weaning of immunosuppression was attempted in patients who did not develop rejection and had normal graft function and month-6 graft biopsy. Tacrolimus was progressively tapered from day 180 to be discontinued by day 270. After day- 270 graft biopsy, MMF was progressively tapered and definitely discontinued by day 365 in the absence of rejection. Results: One patient from the MSC group was excluded from immunosup- pression withdrawal attempt due to HCC recurrence, and the 9 others met the necessary criteria. In one patient, tacrolimus and MMF withdrawal was performed without rejection. In two patients, MMF monotherapy was achieved at month 9, but graft rejection occurred during MMF withdrawal and was successfully treated by tacrolimus reintroduction. In 6 patients, the transam- inases significantly increased during tacrolimus withdrawal. In these cases, withdrawal was cancelled and liver tests normalised after increase of the tacrolimus dose. No graft was lost due to the withdrawal attempt. Conclusion: A single post transplant MSC injection is not sufficient to induce operative tolerance after LT. [less ▲]

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

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

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

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

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See detailInfusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

in Journal of Hepatology (2017)

BACKGROUND & AIM: Mesenchymal stromal cell (MSC) infusion could be a mean to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase-1 study was to evaluate the ... [more ▼]

BACKGROUND & AIM: Mesenchymal stromal cell (MSC) infusion could be a mean to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase-1 study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients. METHODS: Ten liver transplant recipients under standard immunosuppression received 1.5-3x106/kg third-party unrelated MSCs on post-operative day 3+/-2, and were prospectively compared to a control group of 10 liver transplant recipients. As primary end-points, MSC infusional toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary end-points, rejection rate, month-6 graft biopsies, and peripheral blood lymphocyte phenotyping were compared. Progressive immunosuppression weaning was attempted from month 6 to 12 in MSC recipients. RESULTS: No variation in vital parameters or cytokine release syndrome could be detected during and after MSC infusion. No patient developed impairment of organ functions (including liver graft function) following MSC infusion. No increased rate of opportunistic infection or de novo cancer was detected. As secondary end-points, there was no difference in overall rates of rejection or graft survival. Month-6 biopsies did not demonstrate a difference between groups in the evaluation of rejection according to the Banff criteria, in the fibrosis score or in immunohistochemistry (including Tregs). No difference in peripheral blood lymphocyte typing could be detected. The immunosuppression weaning in MSC recipients was not successful. CONCLUSIONS: No side effect of MSC infusion at day 3 after liver transplant could be detected, but this infusion did not promote tolerance. This study opens the way for further MSC or Treg-based trials in liver transplant recipients. LAY SUMMARY: Therapy with mesenchymal stromal cells (MSCs) has been proposed as a mean to improve results of solid organ transplantation. One of the potential MSC role could be to induce tolerance after liver transplantation, i.e. allowing the cessation of several medications with severe side effects. This study is the first-in-man use of MSC therapy in 10 liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression. [less ▲]

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See detailImporting and Exporting Cord Blood Units
BAUDOUX, Etienne ULg; GIET, Olivier ULg; Jöris, Monique et al

Learning material (2016)

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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 ULg; GREGOIRE, Céline ULg; BARON, Frédéric ULg 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 detailClinical - scale expansion of mesenchymal stromal cells: a large banking experience
LECHANTEUR, Chantal ULg; BRIQUET, Alexandra ULg; GIET, Olivier ULg et al

in Journal of Translational Medicine (2016), 14

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn’s disease, solid organ transplantation). As the ... [more ▼]

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn’s disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007. Methods: 68 clinical-grade large-scale MSC cultures were completed and analyzed. The whole process was described, including volunteer donor screening, bone marrow collection, mononuclear cell isolation and expansion over 4 weeks, harvesting, cryopreservation, release, administration and quality controls of the cells (including microbiology, phenotype, and potency assays). Results: From 59 validated donors, 68 cultures were completed (mean of final yields: 886 × 106 cells/culture) and a total of 464 MSC aliquots have been produced and stored in liquid nitrogen (mean of 132.8 × 106 cells/bag). Each MSC batch underwent extensive testing to verify its conformity with EBMT and ISCT release criteria and was individually validated. As of June 1 2015, 314 bags have been released and infused to patients included in 6 different clinical protocols. All thawed MSC units satisfied to release criteria and no infusion-related toxicity was reported. Conclusion: In conclusion, despite low passage cultures, we have been able to create an allogeneic “off-the-shelf” MSC bank with a large number of frozen aliquots and report here an efficient clinical-grade MSC banking activity in place for more than 7 years. Our challenge now is to produce MSC in compliance with good manufacturing practices (GMP) as, in the meantime, MSC have become considered as advanced therapy medicinal products (ATMP). Another significant challenge remains the development of relevant potency assay. [less ▲]

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See detailBone marrow processing for hematopoietic stem cell transplantation: recommendations of the SFGM-TC
Rouard, Hélène; Boulanger, Florence; BAUDOUX, Etienne ULg et al

in Hématologie (2015), 21(Supp 3), 42-46

Le prélèvement de moelle osseuse fait l’objet d’un ou de plusieurs traitements préalablement à son injection au receveur. Ces transformations sont basées sur l’évaluation de la compatibilité ... [more ▼]

Le prélèvement de moelle osseuse fait l’objet d’un ou de plusieurs traitements préalablement à son injection au receveur. Ces transformations sont basées sur l’évaluation de la compatibilité érythrocytaire entre le donneur et le receveur, et sur le volume maximal acceptable du greffon. Elles doivent préserver la quantité de cellules mononucléées et de cellules CD34+ injectées ainsi que leur qualité. Une enquête au sein de centres de thérapie cellulaire francophones a révélé une hétérogénéité, d’une part, des pratiques d’ingénierie cellulaire, en partie liée au marché des automates et, d’autre part, des techniques de titrage des anticorps anti-érythrocytaires et de leur absence de normalisation. Dans une démarche qui vise à uniformiser les pratiques d’allogreffe de cellules souches hématopoïétiques (CSH), la Société franc¸aise de greffe de moelle et de thérapie cellulaire (SFGM-TC) a organisé les cinquièmes ateliers d’harmonisation des pratiques en septembre 2014 à Lille. Nous proposons des recommandations concernant la transformation des greffons de moelle osseuse et les critères de libération [less ▲]

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See detailContrôle de qualité des USP via segments attachés : recommandations de la SFGM-TC
De Vos, John; Birebent, B; Faucher, Catherine et al

in Pathologie et Biologie (2014)

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See detailInfusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease
Hannon, Muriel ULg; LECHANTEUR, Chantal ULg; Lucas, Sophie et al

in Transfusion (2014), 54(February), 353-363

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See detailLarge-Scale Clinical Expansion of Mesenchymal Stem Cells in the GMP-Compliant, Closed Automated Quantum® Cell Expansion System: Comparison with Expansion in Traditional T-Flasks
LECHANTEUR, Chantal ULg; Baila, Stefano; Janssen, Michel Etienne et al

in Journal of Stem Cell Research & Therapy (2014), 4(8), 1000222

Objectives: Significant advances have been achieved regarding the knowledge of the immunoregulatory properties of mesenchymal stem cells (MSC). We are currently involved in several clinical protocols ... [more ▼]

Objectives: Significant advances have been achieved regarding the knowledge of the immunoregulatory properties of mesenchymal stem cells (MSC). We are currently involved in several clinical protocols evaluating these properties in different settings including hematopoietic cells or solid organ transplantation, and severe or refractory autoimmune disorders. Considering the large number of ex-vivo expanded cells required for these clinical protocols (MSC dose varies from 1 to 4x10-6 MSC/kg patient per infusion), we evaluated the Quantum® device, a GMPcompliant, functionally closed, automated hollow fiber bioreactor system and compared it with our traditional clinical culture system in flasks. Methods: Primary and pre-enriched MSC expansions were simultaneously conducted in both culture systems and evaluated in terms of expansion rates and compliance with quality specifications and ISCT-release criteria. Due to practical considerations, most of the experiments conducted in the bioreactor (P1 and P2 expansions) used thawed MSC. These were compared with both fresh and thawed MSC expansions in flasks. Results: The Quantum® device reproducibly produced therapeutic MSC doses that fulfill ISCT-release criteria, are sterile, devoid of mycoplasma and endotoxin, have normal karyotypes and demonstrate immunosuppressive and differentiation capacities in vitro. Cells also grew faster in the bioreactor than in flasks during passage P1 (doubling time 40 compared to 56 hours in flasks) and P2 expansions but not during the primary expansion phase (P0). Seeding 20x10-6 thawed P2-preselected cells on the device allowed us to harvest 110-276x10-6 MSC after a 7 day expansion; seeding 50x10-6 cells resulted in 291-334x10-6 MSC harvested. Conclusion: In conclusion, the Quantum® device is an excellent system to produce a clinical dose of MSC but cost-effectiveness varies as a function of the manufacturing strategy in place. For our particular situation, the use of the Quantum device didn't result in a cost saving solution. [less ▲]

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See detailImpact of cotransplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning
MOERMANS, Catherine ULg; LECHANTEUR, Chantal ULg; BAUDOUX, Etienne ULg et al

in Transplantation (2014), 98(3), 348-353

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal ... [more ▼]

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans. The objective of the study was to investigate the impact of MSC co-infusion on lung function and airway inflammation as well as on the incidence of pulmonary infections and cytomegalovirus (CMV) reactivation after HSCT. Methods: We have prospectively followed 30 patients who underwent unrelated HSCT with MSC co-infusion after non-myeloablative conditioning (NMA). Each patient underwent detailed lung function testing (FEV1, FVC, FEV1/FVC, RV, TLC, DLCO and KCO) and measurement of exhaled nitric oxide before HSCT and 3, 6 and 12 months posttransplant. The incidence of pulmonary infections and CMV reactivation were also monitored. This group was compared with another group of 28 patients who underwent the same type of transplantation but without MSC co-infusion. Results: Lung function tests did not show important modifications over time and did not differ between the MSC and control groups. There was a higher 1-year incidence of infection, particularly of fungal infections, in patients having received a MSC co-infusion. There was no difference between groups regarding the 1-year incidence of CMV reactivation. Conclusions: MSC co-infusion does not induce pulmonary deterioration 1 year after HSCT with NMA conditioning. MSC appear to be safe for the lung but close monitoring of pulmonary infections remains essential. [less ▲]

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See detailThinking out of the box - New approaches to controlling GVHD
Baron, Frédéric ULg; Humblet-Baron, Stéphanie; Ehx, Grégory ULg et al

in Current Hematologic Malignancy Reports (2014), 9

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD ... [more ▼]

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2. [less ▲]

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See detailCleanrooms and tissue banking how happy I could be with either GMP or GTP?
Klykens, J; Pirnay, JP; Verbeken, G et al

in Cell and Tissue Banking (2013)

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See detailEx vivo expansion of hematopoietic progenitor cells is associated with downregulation of alpha4 integrin- and CXCR4-mediated engraftment in NOD/SCID beta2-microglobulin-null mice
Foguenne, Jacques ULg; Di Stefano; Giet, Olivier ULg et al

in Haematologica (2009), 94

Several studies indicate that ex vivo cytokine-supported expansion induces defective hematopoietic stem cell engraftment. We investigated the role of alpha4 integrin, alpha5 integrin and CXCR4 in ... [more ▼]

Several studies indicate that ex vivo cytokine-supported expansion induces defective hematopoietic stem cell engraftment. We investigated the role of alpha4 integrin, alpha5 integrin and CXCR4 in engraftment of unmanipulated and cytokine-treated human cord blood CD34+ cells. [less ▲]

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See detailDespite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice.
Pirson, Laurence ULg; Baron, Frédéric ULg; Meuris, Nathalie ULg et al

in Stem Cells (2006), 24(7), 1814-21

There is potential interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative regimen, to the tyrosine kinase inhibitor imatinib ... [more ▼]

There is potential interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative regimen, to the tyrosine kinase inhibitor imatinib (Glivec; Novartis, Basel, Switzerland, http://www.novartis.com) in order to maximize anti-leukemic activity against Philadelphia chromosome-positive leukemias. However, because imatinib inhibits c-kit, the stem cell factor receptor, it could interfere with bone marrow engraftment. In this study, we examined the impact of imatinib on normal progenitor cell function. Imatinib decreased the colony-forming capacity of mobilized peripheral blood human CD133(+) cells but not that of long-term culture-initiating cells. Imatinib also decreased the proliferation of cytokine-stimulated CD133(+) cells but did not induce apoptosis of these cells. Expression of very late antigen (VLA)-4, VLA-5, and CXCR4 of CD133(+) cells was not modified by imatinib, but imatinib decreased the ability of CD133(+) cells to migrate. Finally, imatinib did not decrease engraftment of CD133(+) cells into irradiated nonobese diabetic/severe combined immunodeficient/beta2m(null) mice conditioned with 3 or 1 Gy total body irradiation. In summary, our results suggest that, despite inhibition of hematopoietic progenitor cell growth in vitro, imatinib does not interfere with hematopoietic stem cell engraftment. [less ▲]

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