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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 Applications of Mesenchymal Cells (in press)

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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 Applications of Mesenchymal Cells (in press)

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See detailInfusion of third-party mesenchymal stromal cells after liver transplantation: a phase 1, open-label, clinical study
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

Poster (2015, March 27)

Transplanted patients have to deal with numerous side effects of life-long dependence on immunosuppressive drugs. Paradoxically these drugs fail to prevent acute and/or chronic rejection in many cases ... [more ▼]

Transplanted patients have to deal with numerous side effects of life-long dependence on immunosuppressive drugs. Paradoxically these drugs fail to prevent acute and/or chronic rejection in many cases. Mesenchymal stromal cells (MSC) are multipotent and self-renewing bone marrow progenitors that have been shown both in vitro and in vivo as capable of (i) immunomodulation, (ii) anti-inflammation in case of ischemia/reperfusion injury, and (ii) stimulation of tissue repair. MSC could therefore be very interesting in organ recipients to limit chronic graft damage and to allow tolerance. This study aimed to be the first clinical evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled, phase I study. Clinical grade MSCs were locally collected from the bone marrow of unrelated healthy donors. They were cultured in a GMP-compliant lab, underwent extensive quality controls and were frozen for storage in a MSC bank. When needed for patient treatment, MSC were thawed and intravenously injected into patients. 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5-3x106/kg MSC on post- operative day 3 ± 2. These patients were prospectively compared to a group of 10 control (MSC-) liver recipients. Primary endpoints were MSC infusion toxicity, and incidence of cancer and opportunistic infections at month 6. Secondary endpoints were patient and graft survivals and rejection at month 6, as well as the effects of MSC on recipients’ immune function and on immunohistology of at month 6 graft biopsies. No MSC infusional toxicity was observed. Both groups were comparable in terms of donor and recipient characteristics. There was no difference in primary end-points between control and MSC groups. No patient developed de novo cancer. There was no statistical difference in patient and graft survivals or in rejection rates. There was no graft rejection in the MSC group. Month-6 graft biopsies were not different according to Banff and fibrosis scores. This phase I study showed excellent tolerability and safety of a single infusion of third-party MSC after liver transplantation. There were no graft safety issues and no excess of immunosuppression after MSC injection. Further analyses of consequences of MSC injection on the immune profile are needed. The possibility of avoiding calcineurin-inhibitors with repeated MSC injections as main immunosuppressive therapy and/of tolerance induction by MSC infusion should be investigated by further studies. [less ▲]

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See detailInfusion of third-party mesenchymal stream cells after liver transplantation: a phase-1, open-label, clinical study
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

in Acta Gastro-Enterologica Belgica (2015, March), 78(1), 29

Background: Mesenchymal stromal cells (MSC) are multipotent bone marrow progenitors that have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aimed ... [more ▼]

Background: Mesenchymal stromal cells (MSC) are multipotent bone marrow progenitors that have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aimed to be the first evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled phase-1 study. This study aimed to be the first evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled phase-1 study. Patients & Methods: Clinical grade MSCs were locally collected from the bone marrow of unrelated healthy donors. They were cultured in a GMP-compliant lab, underwent extensive quality controls and were frozen for storage in a MSC bank. When needed for patient treatment, MSC were thawed and intravenously injected into patients. 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5-3x106/kg MSC on post-operative day 3±2. These patients were prospectively compared to a group of 10 control (MSC-) liver recipients. Primary endpoints were MSC infusion toxicity, and incidence of cancer and opportunistic infections at month 6. Secondary endpoints were patient and graft survivals and rejection at month 6, as well as the effects of MSC on recipients’ immune function and on immunohistology of at month 6 graft biopsies. Results: No MSC infusional toxicity was observed. Both groups were comparable in terms of donor and recipient characteristics. There was no difference in primary end-points between control and MSC groups. No patient developed de novo cancer. There was no statistical difference in patient and graft survivals or in rejection rates. There was no graft rejection in the MSC group. Month-6 graft biopsies were not different according to Banff and fibrosis scores. Discussion: This phase 1 study showed excellent tolerability and safety of a single infusion of third-party MSC after liver transplantation. There were no graft safety issues and no excess of immunosuppression after MSC injection. Further analyses of consequences of MSC injection on the immune profile are needed. The possibility of avoiding calcineurin-inhibitors with repeated MSC injections as main immunosuppressive therapy and/of tolerance induction by MSC infusion should be investigated by further studies. [less ▲]

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See detailCellules stromales mésenchymateuses et transplantation d'organes
DETRY, Olivier ULg; JOURET, François ULg; VANDERMEULEN, Morgan ULg 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 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 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 ULg; GREGOIRE, Céline ULg; Comblain, Fanny ULg 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 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 detailMesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion.
Erpicum, Pauline ULg; DETRY, Olivier ULg; WEEKERS, Laurent ULg et al

in Nephrology Dialysis Transplantation (2014), 29

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of ... [more ▼]

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue. Similarly, at the time of kidney transplantation (KT), I/R is an unavoidable event which contributes to early graft dysfunction and enhanced graft immunogenicity. Mesenchymal stromal cells (MSCs) represent a heterogeneous population of adult, fibroblast-like multi-potent cells characterized by their ability to differentiate into tissues of mesodermal lineages. Because MSC have demonstrated immunomodulatory, anti-inflammatory and tissue repair properties, MSC administration at the time of I/R and/or at later times has been hypothesized to attenuate AKI severity and to accelerate the regeneration process. Furthermore, MSC in KT could help prevent both I/R injury and acute rejection, thereby increasing graft function and survival. In this review, summarizing the encouraging observations in animal models and in pilot clinical trials, we outline the benefit of MSC therapy in AKI and KT, and envisage their putative role in renal ischaemic conditioning. [less ▲]

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

in World journal of gastroenterology : WJG (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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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),

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 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 detailINFUSION OF THIRD-PARTY MESENCHYMAL STEM CELLS (MSC) AFTER KIDNEY AND LIVER TRANSPLANTATION: A PHASE I-II, OPEN-LABEL, CLINICAL STUDY (EudraCT 2011-001822-81 & NCT01429038)
DETRY, Olivier ULg; DELBOUILLE, Marie-Hélène ULg; LECHANTEUR, Chantal ULg et al

Poster (2013, May 30)

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]

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See detailImpact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease
Bruck, France; Belle, Ludovic ULg; LECHANTEUR, Chantal ULg et al

in Cytotherapy (2013), 15(3), 267-279

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous ... [more ▼]

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous studies have suggested that mesenchymal stromal cells (MSCs) could exert potent immunosuppressive effects. Methods. The ability of human bone marrow derived MSCs to prevent xenogeneic GVHD in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice and in NOD/SCID/interleukin-2Rg(null) (NSG) mice transplanted with human peripheral blood mononuclear cells (PBMCs) was assessed. Results. Injection of 200 106 human PBMCs intraperitoneally (IP) into sub-lethally (3.0 Gy) irradiated NOD/SCID mice also given anti-asialo GM1 antibodies IP 1 day prior and 8 days after transplantation induced lethal xenogeneic GVHD in all tested mice. Co-injection of 2 106 MSCs IP on day 0 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Similarly, injection of 30 106 human PBMCs IP into sub-lethally (2.5 Gy) irradiated NSG mice induced a lethal xenogeneic GVHD in all tested mice. Injection of 3 106 MSCs IP on days 0, 7, 14 and 21 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Conclusions. Injection of MSCs did not prevent xenogeneic GVHD in these two humanized mice models. [less ▲]

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See detailInfusion of third party mesenchymal stem cells (MSC) after kidney and liver transplantation: a phase I-II, open-label, clinical study
DETRY, Olivier ULg; DELBOUILLE, Marie-Hélène ULg; LECHANTEUR, Chantal ULg et al

Conference (2012, October 19)

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]

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See detailBone marrow-derived mesenchymal stromal cells failed to prevent experimental xenogeneic graft-versus-host disease
Bruck, France; de Leval, Laurence; Belle, Ludovic ULg et al

Poster (2012)

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See detailCotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.
Baron, Frédéric ULg; Lechanteur, Chantal ULg; Willems, Evelyne ULg et al

in Biology of Blood & Marrow Transplantation (2010), 16(6), 838-47

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD ... [more ▼]

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe. [less ▲]

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See detailThe umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood.
Zeddou, Mustapha ULg; Briquet, Alexandra ULg; Relic, Biserka ULg et al

in Cell Biology International (2010), 34(7), 693-701

Many studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these ... [more ▼]

Many studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these cells can be isolated are still under discussion. Whereas BM (bone marrow) is presented as the main source of MSC, despite the invasive procedure related to this source, the possibility of isolating sufficient numbers of these cells from UCB (umbilical cord blood) remains controversial. Here, we present the results of experiments aimed at isolating MSC from UCB, BM and UCM (umbilical cord matrix) using different methods of isolation and various culture media that summarize the main procedures and criteria reported in the literature. Whereas isolation of MSC were successful from BM (10:10) and (UCM) (8:8), only one cord blood sample (1:15) gave rise to MSC using various culture media [DMEM (Dulbecco's modified Eagle's medium) +5% platelet lysate, DMEM+10% FBS (fetal bovine serum), DMEM+10% human UCB serum, MSCGM] and different isolation methods [plastic adherence of total MNC (mononuclear cells), CD3+/CD19+/CD14+/CD38+-depleted MNC and CD133+- or LNGFR+-enriched MNC]. MSC from UCM and BM were able to differentiate into adipocytes, osteocytes and hepatocytes. The expansion potential was highest for MSC from UCM. The two cell populations had CD90+/CD73+/CD105+ phenotype with the additional expression of SSEA4 and LNGFR for BM MSC. These results clearly exclude UCB from the list of MSC sources for clinical use and propose instead UCM as a rich, non-invasive and abundant source of MSC. [less ▲]

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