Publications (7)18.59 Total impact
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Article: Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of the literature and two pediatric cases.
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ABSTRACT: Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results.We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively).These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients.International Archives of Medicine 08/2011; 4(1):27. -
Article: Sequence polymorphism systems for quantitative real-time polymerase chain reaction to characterize hematopoietic chimerism-high informativity and sensitivity as well as excellent reproducibility and precision of measurement.
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ABSTRACT: Sequence polymorphisms (SPs) can serve as genetic markers for quantitative polymerase chain reactions (qPCR) for chimerism analysis, providing a significantly higher sensitivity compared to short tandem repeat PCR. In this study, a panel of 29 selected markers was evaluated in 317 patients with leukemia and myelodysplastic syndrome, who received allogeneic stem cell transplantation. In total, 5415 posttransplantation samples were analyzed. Recipient genotype discrimination was possible in 96% with a mean number of 2.5 (1-7) informative markers per recipient/donor pair. Marker specific standard dilution series from volunteers' DNA served as standard for quantification of chimerism. Sensitivity of the method was < or =1 x 10-3 (0.1% of recipient cells) in 83.3% of the assays. By this method, it was possible to very accurately detect autologous signals in the range from 0% to 0.5% (95% confidence interval [CI] +/-0.2), from 0.5% to 1% (95% CI +/-0.4), from 1% to 2% (95% CI +/-0.6) and from 2% to 5% (95% CI +/-1.2). Reproducibility of the quantified autologous signals was independent from the amount of DNA. This is the first report on a SP-based chimerism system allowing for the performance of chimerism analyses for virtually all patients with high sensitivity, excellent reproducibility, and precision of measurement.Laboratory Hematology 01/2007; 13(3):73-84. -
Article: Hypericin: a promising fluorescence marker for differentiating between glioblastoma and neurons in vitro.
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ABSTRACT: The naturally occurring photosensitizer, hypericin, with its high quantum yield of singlet oxygen photogeneration was studied for its ability to differentiate between glioblastoma cells and fetal rat neurons using fluorescence microscopy. Eight human glioma cell lines and twelve primary human glioma cell cultures were compared to human astrocytes and cerebellar granule neurons after incubation with 20 microM hypericin for 5-120 min. Photobleaching effects have been studied by exposing the cell lines to 100 msec of excitation light (510-550 wavelength). Mainly, perinuclear hypericin staining was detected. Neurons can be differentiated from glioblastoma cell lines and astrocytes by a lower fluorescence intensity (Tukey-Kramer HSD test, p < 0.0001). Therefore, hypericin seems to be a promising substance for the photodynamic therapy of malignant brain tumors.International Journal of Oncology 12/2005; 27(6):1543-9. · 2.40 Impact Factor -
Article: Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors.
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ABSTRACT: Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with a new CD133-based selection method in 10 paediatric patients with matched unrelated (n = 2) or mismatched-related donors (n = 8). These patients received a combination of stem cells (median = 29.3 x 10(6)/kg), selected with either anti-CD34 or anti-CD133 coated microbeads. The proportion of CD133+ selected cells was gradually increased from patient to patient from 10% to 100%. Comparison of CD133+ and CD34+ separation procedures revealed similar purity and recovery of target populations but a lower depletion of T cells by CD133+ selection (3.7 log vs. 4.1 log, P < 0.001). Both separation procedures produced >90% CD34+/CD133+ double positive target cells. Engraftment occurred in all patients (sustained primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host disease (GvHD) >/= grade II or chronic GvHD was observed. The patients showed a rapid platelet recovery (median time to independence from substitution = 13.5 d), whereas T cell regeneration was variable. Five patients are alive with a median follow-up of 10 months. Our data demonstrates the feasibility of CD133+ selection for transplantation from alternative donors and encourages further trials with total CD133+ separated grafts.British Journal of Haematology 02/2004; 124(1):72-9. · 4.94 Impact Factor -
Article: Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors
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ABSTRACT: Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with a new CD133-based selection method in 10 paediatric patients with matched unrelated (n = 2) or mismatched-related donors (n = 8). These patients received a combination of stem cells (median = 29·3 × 106/kg), selected with either anti-CD34 or anti-CD133 coated microbeads. The proportion of CD133+ selected cells was gradually increased from patient to patient from 10% to 100%. Comparison of CD133+ and CD34+ separation procedures revealed similar purity and recovery of target populations but a lower depletion of T cells by CD133+ selection (3·7 log vs. 4·1 log, P < 0·001). Both separation procedures produced >90% CD34+/CD133+ double positive target cells. Engraftment occurred in all patients (sustained primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host disease (GvHD) ≥ grade II or chronic GvHD was observed. The patients showed a rapid platelet recovery (median time to independence from substitution = 13·5 d), whereas T cell regeneration was variable. Five patients are alive with a median follow-up of 10 months. Our data demonstrates the feasibility of CD133+ selection for transplantation from alternative donors and encourages further trials with total CD133+ separated grafts.British Journal of Haematology 12/2003; 124(1):72 - 79. · 4.94 Impact Factor -
Article: Biology and plasticity of CD133+ hematopoietic stem cells.
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ABSTRACT: AC133 (CD133) is a highly conserved antigen expressed on hematopoietic stem cells with unknown function. In order to further characterize CD133(+) progenitor cells, we purified CD133(+) stem cells using the method of magnetic activated cell sorting (MACS) from healthy adult volunteers mobilized with granulocyte colony-stimulating growth factor (G-CSF) to a mean purity of 94%. The purified CD133(+) cells highly engrafted NOD/SCID mice. In addition, unseparated mononuclear cells or CD133(+) stem cells isolated from the bone marrow of transplanted NOD/SCID mice gave rise to engraftment of secondary recipients. Upon ex vivo culture of purified CD133(+) cells with FLT3/Flk2 ligand (FL) and interleukin-6 (IL-6), a plastic-adherent cell population could be observed after 6 weeks in culture. These adherent cells did not express CD34 or CD133 antigens on their surface, nor did they express markers for endothelial, mesenchymal, or dendritic cells. After incubation of these adherent cells with stem cell factor (SCF), non-adherent cells were observed which partially co-expressed CD133, but were negative for CD34. These nonadherent CD34(-) cells showed a high engraftment capacity in NOD/SCID mice. From our results, we conclude that CD133 might be a marker of early progenitors with a high NOD/SCID engraftment potential. The fact that CD133(+) hematopoietic progenitors can give rise to an adherent population which is CD133(-) and CD34(-) and that these cells can again give rise to a CD133(+)CD34(-) stem cell population with high NOD/SCID engraftment potential indicates the plasticity of hematopoietic precursors. CD133(+) stem cells might be useful for research and for clinical application.Annals of the New York Academy of Sciences 06/2003; 996:141-51. · 3.15 Impact Factor -
Article: CDCP1 is a novel marker for hematopoietic stem cells.
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ABSTRACT: CDCP1 is a transmembrane protein that contains three CUB domains within the extracellular region and a hexalysine stretch within the cytoplasmic region. CDCP1 mRNA is highly expressed in lung and colon tumors and in the erythroleukemic cell line K562. To analyze CDCP1 protein expression, monoclonal antibodies against the extracellular domain of CDCP1 were raised. For this purpose, CDCP1 was overexpressed in NIH-3T3 cells. Balb/c mice were then immunized with the resultant cell line NIH-3T3/huCDCP1. After fusion of SP2/0 cells with immune spleen cells, hybridoma clones were selected that secreted antibodies reacting with NIH-3T3/huCDCP1 cells but not with parental cells. Four antibodies (CUB1-CUB4) were obtained that fulfilled these criteria. Screening of peripheral blood cells revealed that the antibodies did not recognize mature lymphocytes, monocytes, granulocytes, erythrocytes, or platelets. In contrast, multi-color analyses revealed that CDCP1 protein is almost exclusively expressed on a subset of CD34(+) stem/progenitor cells in bone marrow. Transplantation of purified CDCP1(+) cells into NOD/SCID mice resulted in engraftment of human cells with multi-lineage differentiation potential, suggesting that CDCP1 is a novel marker for hematopoietic stem cells.Annals of the New York Academy of Sciences 06/2003; 996:222-6. · 3.15 Impact Factor
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2003
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St. Jude Children's Research Hospital
Memphis, TN, USA
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