Effect in supralethally irradiated rats of granulocyte colony-stimulating factor and lisofylline on hematopoietic reconstitution by syngeneic bone marrow or whole organ passenger leukocytes.
We have previously shown the existence of migratory hematopoietic stem cells in adult solid organs. This study demonstrates that granulocyte colony-stimulating factor (G-CSF) and lisofylline, a phosphatidic acid inhibitor that suppresses hematopoiesis-inhibiting cytokines, can enhance the engraftment of organ-based hematopoietic stem cells. When syngeneic heart grafts or liver nonparenchymal cells were transplanted into lethally irradiated (9.5 Gy) Lewis rats, complete hematopoietic reconstitution and animal survival were significantly improved by treating the recipient with G-CSF or, to a lesser extent, with lisofylline. Pretreatment of hepatic nonparenchymal cell donors with G-CSF, but not lisofylline, also resulted in striking improvement of recipient survival which was associated with an augmented subpopulation of donor stem cells. The results suggest that these drugs can be used to enhance the chimerism that we postulate to be the basis of organ allograft acceptance.
Murase
N
N
Pittsburgh Transplantation Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Ye
Q
Q
Sakamoto
T
T
Terakura
M
M
Demetris
A J
AJ
Thomson
A W
AW
Rao
A
A
Starzl
T E
TE
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016026:Bone Marrow Transplantation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016027:Heart Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D016031:Liver Transplantation; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000037:antagonists & inhibitors*; D051381:Rats; D011917:Rats, Inbred Lew; D014916:Whole-Body Irradiation
D000276:Adjuvants, Immunologic; D010712:Phosphatidic Acids; D016179:Granulocyte Colony-Stimulating Factor; C025189:lisofylline; D010431:Pentoxifylline