Targeted expansion of genetically modified bone marrow cells.
The ability to specifically target a mitogenic signal to a population of genetically modified primary cells would have potential applications both for gene and cell therapy. Toward this end, a gene encoding a fusion protein containing the FK506-binding protein FKBP12, fused to the intracellular portion of the receptor for thrombopoietin (mpl), was introduced into primary murine bone marrow cells. Dimerization of this fusion protein through the addition of a dimeric form of the drug FK506, called FK1012, resulted in a marked proliferative expansion of marrow cells that was restricted to the genetically modified population. FK1012's proliferative effect was sustained and reversible. An apparent preference for differentiation along the megakaryocytic lineage was observed. This approach allows for the specific delivery of a mitogenic signal to a population of genetically modified primary cells and may have applications for studies in hematopoiesis and receptor biology, and for gene and cell therapy.
Jin
L
L
Division of Hematology, Mailstop 357710, Health Sciences Building, University of Washington, Seattle WA 98195, USA. tblau@u.washington.edu
Siritanaratkul
N
N
Emery
D W
DW
Richard
R E
RE
Kaushansky
K
K
Papayannopoulou
T
T
Blau
C A
CA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D019070:Cell Lineage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006360:Heat-Shock Proteins / Q000235:genetics*; D006410:Hematopoiesis / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins / Q000235:genetics; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D022021:Tacrolimus Binding Proteins