Tarte K.,University of Rennes 1 |
Tarte K.,Rennes University Hospital Center |
Gaillard J.,Center Atlantique |
Gaillard J.,University of Tours |
And 14 more authors.
Blood | Year: 2010
Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo. © 2010 by The American Society of Hematology.
PubMed | Center Atlantique, EFS and ANSM
Type: Case Reports | Journal: Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine | Year: 2014
Postdonation information is the knowledge of information about the donor or his donation, occurring after it, which challenges quality or safety of the blood products stemming from this or other donations. Classical hemovigilance sub-processes concerning donors or recipients adverse events do not cover this topic. France is just about to make it official as a fourth sub-process. Less formal management of postdonation information is already set up for more than ten years. French data of the year 2013 are presented, including the regional notification level and the national reporting one. A significant level of heterogeneity is observed as for other hemovigilance sub-processes. It is mainly due to subjective rather than objective differences in risk appreciation. A real consensual work is expected about it in the future.
Delorme B.,French Institute of Health and Medical Research |
Nivet E.,Roche Holding AG |
Nivet E.,French National Center for Scientific Research |
Gaillard J.,French Institute of Health and Medical Research |
And 14 more authors.
Stem Cells and Development | Year: 2010
We previously identified multipotent stem cells within the lamina propria of the human olfactory mucosa, located in the nasal cavity. We also demonstrated that this cell type differentiates into neural cells and improves locomotor behavior after transplantation in a rat model of Parkinson's disease. Yet, next to nothing is known about their specific stemness characteristics. We therefore devised a study aiming to compare olfactory lamina propria stem cells from 4 individuals to bone marrow mesenchymal stem cells from 4 age- and gender-matched individuals. Using pangenomic microarrays and immunostaining with 34 cell surface marker antibodies, we show here that olfactory stem cells are closely related to bone marrow stem cells. However, olfactory stem cells also exhibit singular traits. By means of techniques such as proliferation assay, cDNA microarrays, RT-PCR, in vitro and in vivo differentiation, we report that when compared to bone marrow stem cells, olfactory stem cells display (1) a high proliferation rate; (2) a propensity to differentiate into osseous cells; and (3) a disinclination to give rise to chondrocytes and adipocytes. Since peripheral olfactory stem cells originate from a neural crest-derived tissue and, as shown here, exhibit an increased expression of neural cell-related genes, we propose to name them olfactory ectomesenchymal stem cells (OE-MSC). Further studies are now required to corroborate the therapeutic potential of OE-MSCs in animal models of bone and brain diseases. © Copyright 2010, Mary Ann Liebert, Inc. 2010.
Deschaseaux F.,French National Center for Scientific Research |
Deschaseaux F.,Center Atlantique |
Gaillard J.,Center Atlantique |
Gaillard J.,University of Tours |
And 13 more authors.
FASEB Journal | Year: 2013
Bone-marrow mesenchymal stem cells (MSCs) are the origin of bone-forming cells with immunomodulation potential. HLA-G5 is among the generated immunosuppressive molecules. HLA-G proteins play a crucial role in promoting the acceptance of allografts. However, the mechanisms regulating the expression of HLA-G5 in human MSCs are unknown. We induced differentiation of MSCs and found that HLA-G5 was greatly up-regulated only in osteoblastic cells (+63% for mRNA). Growth plates and bone callus postfracture in adults showed that only bone-lining cells and mesenchymal progenitors were positive for HLA-G5. Use of gene silencing and dominant-negative factors revealed that HLA-G5 depends on the expression and function of the skeletogenesis master genes RUNX2 and DLX5. In addition, HLA-G5 could directly inhibit osteoclastogenesis by acting on monocytes through SHP1. However, in mature osteoblasts, the expression of HLA-G5 protein was greatly suppressed whereas the proosteoclastogenic factor, RANKL, was concomitantly increased. Down-regulation of HLA-G5 expression during the maturation of osteoblasts was due to binding of the repressor GLI3, a signal transducer of the Hedgehog pathway, to the GLI binding element within the HLA-G promoter. Our findings show that mesenchymal progenitors and osteoblastic cells specifically express HLA-G5 during osteogenesis, with a key role in bone homeostasis. © FASEB.
Lemee J.-M.,University of Angers |
Petit D.,University of Angers |
Splingard M.,Center Atlantique |
Menei P.,University of Angers
Neurochirurgie | Year: 2013
Background and purpose: Decompressive craniectomy is the most common justification for cranioplasty. A medico-economial study based on the effective cost of the hydroxyapatite prosthesis, the percentage of autologous bone graft's loss due to bacterial contamination and the healthcare reimbursment, will allow us to define the best strategy in term of Healthcare economy management for the cranioplasties. A comparison was made between the two groups of patients, autologous bone flap versus custom-made prosthesis in first intention, based on the clinical experience of our department of neurosurgery. Results: No differences was shown between the two groups of patients, in terms of lenght of in-hospital stay and population's characteristics or medical codification. The mean cost of a cranioplasty using the autologous bone graft in first intention was €. 4045, while the use of hydroxyapatite prosthesis led to a cost of €. 8000 per cranioplasty. Conclusion: In term of Healthcare expenses, autologous bone flap should be used in first intention for cranioplasties, unless the flap is contaminated or in specific indications, when the 3D custom-made hydroxyapatite prosthesis should be privilegied. © 2012 Elsevier Masson SAS.
PubMed | Center atlantique, Laboratoire Of Therapie Cellulaire, Institute Paoli Calmettes, Nancy University Hospital Center and University Pierre and Marie Curie
Type: Journal Article | Journal: Pathologie-biologie | Year: 2014
Thousands of autologous and at less extent allogeneic hematopoietic stem cells (HSC) bags are cryopreserved in France. The majority of autologous HSC grafts are used within a year after collection. However, many bags are still unused and cryopreserved for many years. In France and on a European scale, the ever-growing number of cryopreserved bags represents a real economic health concern. Indeed, the cost of storage is about 100 per bag and per year. In addition, quality and therapeutic value of these long-term cryopreserved grafts needs to be evaluated. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from its member centers across France. These workshops took place in September 2013 in Lille. In this article, we addressed the issue of the destruction of long-term cryopreserved grafts be them autologous or allogeneic and provide recommendations regarding their destruction.
PubMed | Center Atlantique and French National Center for Scientific Research
Type: | Journal: Stem cell research & therapy | Year: 2015
Mesenchymal stem cells (MSC) are well described for their role in tissue regeneration following injury. Migratory properties of endogenous or administrated MSC are critical for tissue repair processes. Platelet-derived growth factor (PDGF) is a chemotactic growth factor that elicits mesenchymal cell migration. However, it is yet to be elucidated if signaling pathways other than direct activation of PDGF receptor (PDGF-R) are involved in PDGF-induced cell migration.Knocking down and co-immunoprecipitation approaches were used to evaluate urokinase-type plasminogen activator receptor (uPAR) requirement and its interactions with proteins involved in migration mechanisms, in human MSC induced to migrate under PDGF-AB effect.We demonstrated that uPAR activation and its association with 1-integrin are required for PDGF-AB-induced migration. This phenomenon takes place in MSC derived from bone marrow and from adipose tissue.We showed that PDGF-AB downstream signaling requires other effector molecules in MSC such as the uPA/uPAR system and 1 integrin signaling pathway known for their role in migration. These findings provide new insights in molecular mechanisms of PDGF-AB-induced migration of human MSC that may be relevant to control MSC function and tissue remodeling after injury.
Le Nail L.-R.,University of Tours |
Le Nail L.-R.,University of Nantes |
Stanovici J.,University of Tours |
Stanovici J.,University of Nantes |
And 5 more authors.
International Orthopaedics | Year: 2014
Purpose: Tibial fractures are the most common lower limb fractures. Some criteria such as open fractures and increasing open stage are known to be associated with high delayed union and pseudarthrosis rate. In cases of delayed or nonunion, classical treatment is autologous cancelous bone graft which is associated with high morbidity rate. The ideal treatment would be a percutaneous harvesting and grafting technique. As bone marrow autologous concentrate (BMAC) presents both advantages, we evaluated this technique from 2002 to 2007. Methods: This was a retrospective study of 43 cases of open tibial fractures with initial surgical treatment. The criteria of inclusion were open fracture and nonunion, delayed union or suspicion of delayed union. Results: In 23 cases (53.5 %) BMAC was successful. The success group had received significantly more CFU-F than the failure group (469 vs 153.103, p=0.013). A threshold of 360.103 CFU-F grafted could be established over which there was 100 % success. BMAC done before 110 days after fracture had 47 % success and BMAC done since 110 days after fracture had 73 % success. BMAC success rate decreased with increasing initial fracture skin open stage. There was no BMAC success in cases of a fracture with a remaining gap of more than 4 mm. We had no complications with the technique at the iliac harvesting zone and tibia injection point. Conclusion: BMAC is a technique that should be considered as one of the different alternatives for management of long-bone delayed and nonunion because of its effectiveness, low complication rate, preservation of bone stock and low cost. © 2014 Springer-Verlag.
PubMed | Center Atlantique, Banque de sang, Sanguine, Laboratoire dhematologie and 3 more.
Type: Journal Article | Journal: Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine | Year: 2014
Malaria endemic status of our countries supports avoiding malaria screening for the blood qualification. But this attitude makes young children, pregnant women and people without semi-immunity incur a high risk of malaria. The goal of the survey was to value the reality and the importance of transfusion-transmitted malaria and to assess its determining factors. The study included 141packed-red-cells units transfused to 77hospitalized recipients, not suffering from malaria and not having been transfused the last two weeks. Every packed-red-cells assigned to a patient was tested for malaria before use. Thick and thin blood film were performed 96hours after transfusion. A clinical follow-up was undertaken as well as in the hospital and at home after release. In all, 13.47% of the transfused packed-red-cells were positive for the thick blood film. Plasmodium research in patients was negative 96hours after transfusion, even in the 19patients who had received parasitized blood units! The home follow-up had permitted to note that 15.78% of blood recipients had developed clinical malaria. Parasitic density 240parasites/mm(3) seems to be a determining factor. Transfusion-transmitted malaria is a reality we ought to consider. Introduction of malaria screening in donated blood qualification testings simultaneously with a framing of the blood donors appear the lasting solution to hope in the future to limit the waited excessive blood evictions.
Immunological blood transfusion safety and selection of red blood cells issued from hospital blood banks [Choix des concentrés érythrocytaires délivrés par les dépôts et sécuritétransfusionnelle immunologique]
Py J.-Y.,Center Atlantique
Transfusion Clinique et Biologique | Year: 2010
Allogeneic red blood cells transfusion is always an immunological challenge and the choice of the blood products is crucial for the patient safety. But this choice may be hampered by the quality or the quantity of the available supply. In the end, the lack of transfusion may be more harmful than transfusion. The balance between patients' needs and blood centres supplying is always delicate. The conditions are not the same for all blood groups. Things are easier for the KEL1 phenotype, where the supply must ensure only 92.5% of KEL: -1 red blood cells instead of the 91% expected. More complicated is the situation for group O red blood cells with 47 versus 43%. But the major problem concerns RH: -1 red blood cells, for which the needs reach 20.1 versus 15%. These challenges require a lot of efforts from blood centres staffs to influence blood donors' recruitment and appointments. A justified and carefully selected blood products issuing may be of great help, especially for group O RH: -1 red blood cells. Therefore, hospital blood banks must have ad hoc procedures and a trained staff to put them into practice. © 2010 Elsevier Masson SAS.