title: Genetic modification of mesenchymal stem cells to overexpress CXCR4 and CXCR7 does not improve the homing and therapeutic potentials of these cells in experimental acute kidney injury.
abstract: The therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in kidney failure has been examined in some studies. However, recent findings indicate that after transplantation, these cells home to kidneys at very low levels. Interaction of stromal derived factor-1 (SDF-1) with its receptor, CXCR4, is of pivotal importance in migration and homing. Recently, CXCR7 has also been recognized as another SDF-1 receptor that interacts with CXCR4 and modulates its functions. In this study, CXCR4 and CXCR7 were separately and simultaneously overexpressed in BALB/c bone marrow MSCs by using a lentiviral vector system and the homing and renoprotective potentials of these cells were evaluated in a mouse model of cisplatin-induced acute kidney injury. Using flow cytometry, immunohistochemistry, and real-time PCR methods for detection of GFP-labeled MSCs, we found that although considerably entrapped in lungs, native MSCs home very rarely to kidneys and bone marrow and this rate cannot be significantly affected by CXCR4 and/or CXCR7 upregulation. Transplantation of neither native nor genetically engineered MSCs ameliorated kidney failure. We concluded that overexpression of CXCR4 and CXCR7 receptors in murine MSCs cannot improve the homing and therapeutic potentials of these cells and it can be due to severe chromosomal abnormalities that these cells bear during ex vivo expansion.
authors.affiliation: Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Yousof
authors.initials: Y
authors.lastname: Gheisari
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Naser
authors.initials: N
authors.lastname: Ahmadbeigi
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Nassiri
authors.forename: Azadeh Fahim
authors.initials: AF
authors.lastname: Golestaneh
authors.forename: Mahmood
authors.initials: M
authors.lastname: Naderi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Vasei
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
authors.forename: Siamak
authors.initials: S
authors.lastname: Mirab-Samiee
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement; D002469:Cell Separation; D002945:Cisplatin; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D054387:Receptors, CXCR / Q000235:genetics* / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000627:therapeutic use; D015203:Reproducibility of Results; D016019:Survival Analysis; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000235:genetics
chemical_list: C514936:CXCR4 protein, mouse; C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins; D002945:Cisplatin