Effect of tresperimus on ex vivo expansion of CD34+CD38(-)-enriched cord blood cells.
Tresperimus, an analogue of 15-deoxyspergualine (15-DSG), has been found, in rodents, to induce a potent state of tolerance after organ and bone marrow allografts. In a previous study, we have reported that tresperimus at the optimal concentration of 0.5 microgram/ml supports the clonogenic potential of human cord blood CD34+ cells. Dose dependent inhibition of clonogenesis was also observed with complete reversibility following drug withdrawal. In this study, we tested the effect of 0.5 microgram tresperimus/ml on ex vivo expansion of primitive human cord blood CD34+CD38- cells. Our findings revealed that the total number of expanded cells was decreased in the presence of tresperimus. However, the multipotential and erythroid colonies were significantly increased in the presence of tresperimus compared with control cultures done without the test drug. Progenitor cell morphology was comparable in both test and control cultures. The telomerase activity was consistently lower in tresperimus-treated hematopoietic progenitors than in control cultures. These results suggest that tresperimus preserves primitive CD34+CD38- cells in a state of high potentiality while limiting the total number of their differentiated progeny. Bearing in mind that the test drug supports the clonogenic potential of CD34+ cells, the overall findings emphasize the importance of assessing the effect of tresperimus on in vivo long-term hematopoiesis which could predict the potential clinical use of tresperimus in the prevention of graft-versus-host disease in recipients of allogeneic bone marrow.
el Marsafy
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Laboratoire de Recherche sur la Biologie de la Moelle Osseuse, Institut Universitaire d'Hématologie, EA 1814 Paris VII, Hôpital Saint Louis, 1, Avenue Claude Vellefaux, 75475 Paris, France. sanaaelmarsafy@yahoo.com
Dutartre
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Gluckman
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D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008562:Membrane Glycoproteins; D019098:Telomerase / Q000096:biosynthesis; D014184:Transplantation, Homologous
D015703:Antigens, CD; D018952:Antigens, CD34; D002219:Carbamates; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; C092303:tresperimus; D019098:Telomerase; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1