title: Transgene expression study of CXCR4 active mutants. Potential prospects in up-modulation of homing and engraftment efficiency of hematopoietic stem/progenitor cells.
abstract: Homing and engraftment, a determining factor in hematopoietic stem cell transplantation success is defined as a process through which hematopoietic stem/progenitor cells (HSPCs) lodge recipient bone marrow. SDF-1/CXCR4 axis acts as a principle regulator in homing and engraftment, however, CXCR4 signaling is dependent upon expression of CXCR4 and its ligand SDF-1, which is highly dynamic. Hence, present investigation was aimed to explore the potential of CXCR4 constitutive active mutants (CXCR4-CAMs) in overcoming the limitation of CXCR4 signaling and up-modulate its efficiency in homing and engraftment. Regulated transgene expression study of these mutants revealed their significantly enhanced cell adhesion efficiency to endothelium and extracellular matrix protein. This altogether indicates promising prospects of CXCR4-CAMs in research aimed to improve HSPCs engraftment efficiency.
authors.affiliation: a Stem Cell & Gene Therapy Research Group ; Institute of Nuclear Medicine & Allied Sciences ; Delhi , India.
authors.forename: Menka
authors.initials: M
authors.lastname: Sharma
authors.forename: Farhat
authors.initials: F
authors.lastname: Afrin
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Tripathi
authors.forename: Gurudutta
authors.initials: G
authors.lastname: Gangenahalli
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D020014:K562 Cells; D019718:Receptors, CXCR4 / Q000235:genetics*; D015398:Signal Transduction; D019076:Transgenes
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
keywords: Ala, Alanine; Asn, Asparagine; BM, Bone Marrow; BMEC, Bone marrow endothelial cells; BSA, Bovine Serum Albumin; CAMs, Constitutive Active Mutants; CXCR4; Conc., Concentration; ECM, Extracellular matrix; FBS, Fetal Bovine Serum; FN, Fibronectin; HSPCs; HSPCs, Hematopoietic Stem/ Progenitor Cells; HUVECs, Human Umbilical Vein Endothelial cells; IMDM, Iscove's Modified Dulbecco Media; LIF, Leukemia Inhibitory Factor; MCS, Multi Cloning Site; Ser, Serine; TM3, Transmembrane three domain; engraftment; homing