title: Bcl-XL expression in stem cells facilitates engraftment and reduces the need for host conditioning during bone marrow transplantation.
abstract: 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.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Marielena
authors.initials: M
authors.lastname: Mata
authors.forename: Elise
authors.initials: E
authors.lastname: Chiffoleau
authors.forename: Scott H
authors.initials: SH
authors.lastname: Adler
authors.forename: Tynua
authors.initials: T
authors.lastname: Gray
authors.forename: Wayne
authors.initials: W
authors.lastname: Hancock
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
mesh_terms: 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
chemical_list: C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein