Bcl-XL expression in stem cells facilitates engraftment and reduces the need for host conditioning during bone marrow transplantation.
The prolonged survival of donor hematopoietic stem cells is crucial to the success of bone marrow transplantation. The anti-apoptotic gene Bcl-xL has been shown to promote survival of cells of the erythroid, myeloid and lymphoid lineages. To evaluate a potential therapeutic role for Bcl-xL, we used a retroviral vector to express Bcl-xL in donor cells used for murine bone marrow transplantation. We find that Bcl-xL expression in bone marrow cells facilitates hematopoietic reconstitution (as assessed by total cellularity) without altering cell differentiation. Most importantly, cells reconstituted with Bcl-xL are able to achieve high levels of donor chimerism even in non-ablative conditioning protocols in a syngeneic model of transplantation. Thus, expression of Bcl-xL by donor cells during bone marrow transplantation may provide a means to minimize host conditioning and toxicity while still achieving therapeutic degrees of mixed chimerism.
Mata
Marielena
M
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Chiffoleau
Elise
E
Adler
Scott H
SH
Gray
Tynua
T
Hancock
Wayne
W
Turka
Laurence A
LA
D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation / Q000379:methods*; D002470:Cell Survival; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism*; D019172:Transplantation Conditioning; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein