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Fekete N.,Universitatsklinikum Ulm | Fekete N.,University of Ulm | Fekete N.,University of Twente | Erle A.,Universitatsklinikum Ulm | And 14 more authors.
Tissue Engineering - Part C: Methods | Year: 2015

Cell therapy using multipotent mesenchymal stromal cells (MSCs) is of high interest in various indications. As the pleiotropic effects mediated by MSCs rely mostly on their unique secretory profile, long-term persistence of ex-vivo-expanded cells in the recipient may not always be desirable. Irradiation is a routine procedure in transfusion medicine to prevent long-term persistence of nucleated cells and could therefore also be applied to MSCs. We have exposed human bone-marrow-derived MSCs to 30 or 60 Gy of γ-irradiation and assessed cell proliferation, clonogenicity, differentiation, cytokine levels in media supernatants, surface receptor profile, as well as expression of proto-oncogenes/cell cycle markers, self-renewal/stemness markers, and DNA damage/irradiation markers. Irradiated MSCs show a significant decrease in proliferation and colony-forming unit-fibroblasts. However, a subpopulation of surviving cells is able to differentiate, but is unable to form colonies after irradiation. Irradiated MSCs showed stable expression of CD73 and CD90 and absence of CD3, CD34, and CD45 during a 16-week follow-up period. We found increased vascular endothelial growth factor (VEGF) levels and a decrease of platelet-derived growth factor (PDGF)-AA and PDGF-AB/BB in culture media of nonirradiated cells. Irradiated MSCs showed an inverse pattern, that is, no increase of VEGF, and less consumption of PDGF-AA and PDGF-AB/BB. Interestingly, interleukin-6 (IL-6) levels increased during culture regardless of irradiation. Cells with lower sensitivity toward γ-irradiation showed positive β-galactosidase activity 10 days after irradiation. Gene expression of both irradiated and nonirradiated MSCs 13-16 weeks after irradiation with 60 Gy predominantly followed the same pattern; cell cycle regulators CDKN1A (p21) and CDKN2A (p16) were upregulated, indicating cell cycle arrest, whereas classical proto-oncogenes, respectively, and self-renewal/stemness markers MYC, TP53 (p53), and KLF4 were downregulated. In addition, DNA damage/irradiation markers ATM, ATR, BRCA1, CHEK1, CHEK2, MDC1, and TP53BP1 also mostly showed the same pattern of gene expression as high-dose γ-irradiation. In conclusion, we demonstrated the existence of an MSC subpopulation with remarkable resistance to high-dose γ-irradiation. Cells surviving irradiation retained their trilineage differentiation capacity and surface marker profile but changed their cytokine secretion profile and became prematurely senescent. Copyright 2015, Mary Ann Liebert, Inc. Source


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. Source


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. Source


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. Source


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. Source

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