Caspase inhibitor ZVAD-fmk facilitates engraftment of donor hematopoietic stem cells in intra-bone marrow-bone marrow transplantation.
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.
Imai
Yuichiro
Y
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Adachi
Yasushi
Y
Shi
Ming
M
Shima
Chieko
C
Yanai
Seiji
S
Okigaki
Mitsuhiko
M
Yamashima
Tetsumori
T
Kaneko
Kazunari
K
Ikehara
Susumu
S
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
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