Effect of tresperimus on in vitro human cord blood CD34+ cell differentiation.
Tresperimus, an analogue of 15-deoxyspergualin (15-DSG), is immunosuppressive and prevents lethal graft-versus-host disease following allogeneic bone marrow transplantation in mice. Here, we present an in vitro dose response study examining the ability of tresperimus to support clonogenesis in cultured CD34+ cord blood stem cells. Our findings revealed that only the lowest dose examined, 0.5 microg tresperimus/ml, supports normal myelopoiesis, erythropoiesis and megakaryopoiesis. Greater concentrations of the drug induced dose-dependent inhibition of clonogenesis. This latter effect was not due to apoptosis and was reversible by drug withdrawal. We conclude that tresperimus at 0.5 microg/ml supports the clonogenic potential of cord blood CD34+ cells. Dose-dependent inhibition of clonogenesis was completely reversible following drug withdrawal. These results may be of clinical interest as tresperimus is currently used in phase I-III studies for the prevention of graft versus host disease in recipients of allogeneic bone marrow.
El Marsafy
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S
Laboratoire de Recherche sur la Biologie de la Moelle Osseuse, Institut Universitaire d'Hématologie, Hĵpital Saint Louis, Paris, France. sanaaelmarsafy@yahoo.com
Dutartre
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P
Gluckman
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E
D018952:Antigens, CD34 / Q000097:blood*; D017209:Apoptosis / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology
D018952:Antigens, CD34; D002219:Carbamates; D007166:Immunosuppressive Agents; C092303:tresperimus; D013926:Thrombopoietin