title: Caspase inhibitor ZVAD-fmk facilitates engraftment of donor hematopoietic stem cells in intra-bone marrow-bone marrow transplantation.
abstract: When bone marrow transplantation (BMT) is carried out, survival of the donor hematopoietic stem cells is crucial to maintain donor hematopoiesis in the recipients. We have shown that intra-bone marrow-bone marrow transplantation (IBM-BMT) can induce the rapid recovery of donor hematopoiesis and allow a reduction in radiation doses as a pretreatment for BMT. If IBM-BMT methodology can be further improved, BMT could be carried out more safely and more easily. In this experiment, we attempted to suppress apoptosis of donor hematopoietic cells using a caspase inhibitor, ZVAD-fmk, upon IBM-BMT in mouse allogeneic IBM-BMT. IBM-BMT with ZVAD-fmk induced superior engraftment of donor hematopoietic cells and greater numbers of day-12 colony-forming units of spleen (CFU-S) than IBM-BMT without ZVAD-fmk upon allogeneic BMT (C57BL/6 into BALB/c mice). ZVAD-fmk slightly suppressed apoptosis of whole BMCs, whereas it significantly suppressed apoptosis of c-kit+/Sca-1+/lineage(-) cells (KSL cells) in vitro. These results suggest that ZVAD-fmk can suppress apoptosis of hematopoietic stem cells and/or immature progenitor cells of the donor bone marrow cells, thereby accelerating the donor hematopoiesis.
authors.affiliation: First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Imai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Chieko
authors.initials: C
authors.lastname: Shima
authors.forename: Seiji
authors.initials: S
authors.lastname: Yanai
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Okigaki
authors.forename: Tetsumori
authors.initials: T
authors.lastname: Yamashima
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D017209:Apoptosis; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods; D061945:Caspase Inhibitors; D019070:Cell Lineage; D049109:Cell Proliferation; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage; D006082:Graft Enhancement, Immunologic; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011879:Radiotherapy Dosage; D019089:Stem Cell Factor / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000950:Antigens, Ly; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019089:Stem Cell Factor; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone