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Publications (9)41.28 Total impact

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    ABSTRACT: Human skeletal muscle is an essential source of various cellular progenitors with potential therapeutic perspectives. We first used extracellular markers to identify in situ the main cell types located in a satellite position or in the endomysium of the skeletal muscle. Immunohistology revealed labeling of cells by markers of mesenchymal (CD13, CD29, CD44, CD47, CD49, CD62, CD73, CD90, CD105, CD146, and CD15 in this study), myogenic (CD56), angiogenic (CD31, CD34, CD106, CD146), hematopoietic (CD10, CD15, CD34) lineages. We then analysed cell phenotypes and fates in short- and long-term cultures of dissociated muscle biopsies in a proliferation medium favouring the expansion of myogenic cells. While CD56(+) cells grew rapidly, a population of CD15(+) cells emerged, partly from CD56(+) cells, and became individualized. Both populations expressed mesenchymal markers similar to that harboured by human bone marrow-derived mesenchymal stem cells. In differentiation media, both CD56(+) and CD15(+) cells shared osteogenic and chondrogenic abilities, while CD56(+) cells presented a myogenic capacity and CD15(+) cells presented an adipogenic capacity. An important proportion of cells expressed the CD34 antigen in situ and immediately after muscle dissociation. However, CD34 antigen did not persist in culture and this initial population gave rise to adipogenic cells. These results underline the diversity of human muscle cells, and the shared or restricted commitment abilities of the main lineages under defined conditions.
    Experimental Cell Research 09/2010; 316(15):2513-26. · 3.56 Impact Factor
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    ABSTRACT: Fanconi anemia (FA) is a rare condition due to the genetic inactivation of the FA/BRCA pathway. During childhood, most FA patients display progressive bone marrow failure (BMF), the mechanism of which has not been clarified to date. We analyzed BM mesenchymal stem cells (MSCs) from a series of 20 FA patients with BMF (patient median age 12.5 years old, range 7-34). Expression of FANCD2 and sensitivity to mitomycin C, differentiation capacities, and hematopoiesis-supporting abilities, as well as proliferation, cell senescence, and telomere length were assessed. FA MSCs demonstrated hypersensitivity to mitomycin C compared to control MSCs, as expected for FA cells. FA MSCs had normal immunophenotype, support long-term culture of hematopoietic stem cells (HSCs), and display normal differentiation capacities. Telomere loss during cell aging was similar for FA and control MSCs. However, FA MSCs showed reduced long-term proliferation ability, higher stem cell factor and interleukin-6 levels, and increased expression of senescent-associated beta-galactosidase compared to normal MSCs, suggesting a potential role of the BM microenvironment in long-term BMF.
    Stem cells and development 08/2009; 19(2):203-8. · 4.15 Impact Factor
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    ABSTRACT: Allogeneic bone marrow (BM) transplant (BMT) outcomes have been correlated with the infused nucleated, CD34(+), and T- cell dose. The potential impact of natural killer (NK) BM infused cell dose has however not been established. We analysed the outcomes of 78 patients receiving an HLA identical BMT. A higher NK cell dose was associated with the speed of neutrophil (P = 0.05) and platelet recovery (P = 0.04). Higher nucleated cells, CD34(+), CD3(+), CD3(+)/4(+), CD3(+)/8(+) and NK cell dose were associated with a lower incidence of chronic GvHD (cGvHD) in univariate analysis. In multivariate analysis, the risk of cGvHD was increased by a lower NK cell dose [hazard ratio (HR) = 2.3 (1.2-4.4) for cell dose <0.9 x 10(6)/kg; P = 0.01] and an older age [HR = 1.4 /10 years (1.1-1.8); P = 0.002]. In addition, a higher CD3(+)/4(+) and NK cell dose were associated with a decreased incidence of viral infections (P = 0.03 and P = 0.06 respectively). No specific cell subpopulation infused dose was associated with survival. In conclusion, a higher BM NK cell dose is associated with an increased speed of neutrophil recovery and a decreased incidence of cGvHD.
    British Journal of Haematology 07/2007; 138(1):101-9. · 4.94 Impact Factor
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    ABSTRACT: We described the ex vivo production of mature and functional human smooth muscle cells (SMCs) derived from skeletal myoblasts. Initially, myoblasts expressed all myogenic cell-related markers such as Myf5, MyoD and Myogenin and differentiate into myotubes. After culture in a medium containing vascular endothelial growth factor (VEGF), these cells were shown to have adopted a differentiated SMC identity as demonstrated by alphaSMA, SM22alpha, calponin and smooth muscle-myosin heavy chain expression. Moreover, the cells cultured in the presence of VEGF did not express MyoD anymore and were unable to fuse in multinucleated myotubes. We demonstrated that myoblasts-derived SMCs (MDSMCs) interacted with endothelial cells to form, in vitro, a capillary-like network in three-dimensional collagen culture and, in vivo, a functional vascular structure in a Matrigel implant in nonobese diabetic-severe combined immunodeficient mice. Based on the easily available tissue source and their differentiation into functional SMCs, these data argue that skeletal myoblasts might represent an important tool for SMCs-based cell therapy.
    Experimental Cell Research 05/2007; 313(7):1337-46. · 3.56 Impact Factor
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    ABSTRACT: In allogeneic bone marrow transplantation (BMT), a higher nucleated and CD34+ cell dose has been reported to improve various outcomes. Other cell types, such as lymphocyte subsets, also influenced BMT results. While nucleated red blood cells (NRBCs) represent a subset of bone marrow (BM) cell subpopulation, the question of their quantification in BM grafts and the impact of BM processing on their recovery has not been addressed. In a prospective study on 77 BM products, NRBCs were enumerated by flow cytometry and the recovery analyzed after manipulation. Because NRBCs could compromise white blood cell count, the impact of NRBC count on CD34+ cell percentage and total nucleated cell (TNC) dose were also determined. The mean percentage of NRBCs in BM grafts was 21.6 percent (range, 7.8%-40.9%). Mean NRBC recoveries after BM concentration or RBC depletion were 98.4 and 28.7 percent, respectively, close to those obtained for TNC cells (88.6 and 31.3%, respectively). When corrected with NRBC count, the mean percentages of corrected CD34+ cell and TNC dose were significantly modified when compared with uncorrected values, whatever the type of BM manipulation. Our data show that NRBC quantification might be of importance to improve quality control of BM products and to evaluate the influence of NRBCs cell dose on outcomes after BMT.
    Transfusion 03/2007; 47(2):266-71. · 3.53 Impact Factor
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    ABSTRACT: Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells, primarily in the bone marrow (BM). The role of the BM microenvironment in the pathogenesis of the disease has been demonstrated, especially for the survival and growth of the myeloma plasma cells. Functional characterization of the major component of the BM microenvironment, namely the recently characterized mesenchymal stem cells (MSCs), was never performed in MM. Based on a series of 61 consecutive patients, we evaluated the ability of MSCs derived from myeloma patients to differentiate into adipocytes and osteocytes, inhibit T-cell functions, and support normal hematopoiesis. MSCs phenotypic characterization and quantification of interleukin-6 (IL-6) secretion were also performed. As compared to normal MSCs, MSCs from MM patients exhibited normal phenotype, differentiation capacity and long-term hematopoietic support, but showed reduced efficiency to inhibit T-cell proliferation and produced abnormally high amounts of IL-6. Importantly, these characteristics were observed in the absence of any detectable tumor plasma cell. Chromosomal analysis revealed that MM patients MSCs were devoid of chromosomal clonal markers identified in plasma cells. MM MSCs present abnormal features that may participate in the pathogenesis of MM.
    Leukemia 02/2007; 21(1):158-63. · 10.16 Impact Factor
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    ABSTRACT: Red cell (RBC) depletion is needed to bypass ABO mismatch in allogeneic bone marrow transplantation (BMT). Technical and clinical data obtained after bone marrow (BM) processing with a continuous-flow cell separator (Cobe Spectra, Gambro BCT) are reported. RBC depletion and recovery of nucleated cells, CD3+ cells, CD34+ cells, and colony-forming unit-granulocyte-macrophage were calculated. Bacteriologic contaminations, side effects of graft infusion, and hematopoietic recovery were analyzed. A total of 114 BM samples were processed. The mean volume collected was 1099 mL (range, 390-2450 mL). Initial and residual mean RBCs volumes were 309.9 and 4.0 mL corresponding to a depletion of 98.6 +/- 0.78 percent. Before processing, the mean numbers of nucleated cells, granulocytes, CD3+ cells, CD34+ cells, and CFU-GM were 20.28 x 10(9), 12.79 x 10(9), 1.96 x 10(9), 356.7 x 10(6), and 195.6 x 10(5), respectively. The mean corresponding recoveries after processing were 33.66, 48.98, 82.02, 82.2, and 93.9 percent. Limited side effects were observed in 14 patients without correlation with residual RBCs volume. All but two patients engrafted. BM processing with the Cobe Spectra cell separator provides high rates of RBC depletion without significant side effects after BMT.
    Transfusion 04/2006; 46(3):398-402. · 3.53 Impact Factor
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    ABSTRACT: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by a typical regional distribution, featuring composed patterns of clinically affected and unaffected muscles. No treatment is available for this condition, in which the pathophysiological mechanism is still unknown. Autologous transfer of myoblasts from unaffected to affected territories could be considered as a potential strategy to delay or stop muscle degeneration. To evaluate the feasibility of this concept, we explored and compared the growth and differentiation characteristics of myoblasts prepared from phenotypically unaffected muscles of five FSHD patients and 10 control donors. According to a clinically approved procedure, 10(9) cells of a high degree of purity were obtained within 16-23 days. More than 80% of these cells were myoblasts, as demonstrated by labeling of the muscle markers CD56 and desmin. FSHD myoblasts presented a doubling time equivalent to that of control cells; they kept high proliferation ability and did not show early telomere shortening. In vitro, these cells were able to differentiate and to express muscle-specific antigens. In vivo, they participated to muscle structures when injected into immunodeficient mice. These data suggest that myoblasts expanded from unaffected FSHD muscles may be suitable tools in view of autologous cell transplantation clinical trials.
    Gene Therapy 12/2005; 12(22):1651-62. · 4.32 Impact Factor
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    ABSTRACT: Umbilical cord blood T cells are less functional. Different explanations have been proposed. In this study we analyze the Vbeta T cell cord blood repertoire. All the Vbeta families are expressed. We found only the overexpression of three Vbeta: Vbeta 5-1, Vbeta 5-2, Vbeta 21-2.
    Bone Marrow Transplantation 08/1998; 22 Suppl 1:S39-40. · 3.54 Impact Factor