Characterization and biodistribution of human mesenchymal stem cells transduced with lentiviral-mediated BMP2 |
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Authors: | Kyoung Suk Choi Soon Young Ahn Tek Seung Kim Jiseon Kim Byoung-Guk Kim Kyung Ho Han Sang Ja Ban Hyung Soo Kim Youngju Choi Chul-Joo Lim |
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Institution: | (1) Department of Pharmacology, Division of Gene Therapy, Center for Gene Therapy, Tulane National Primate Research Center, Tulane UniversityHealth Sciences Center, 18703 Three Rivers Road, Covington, LA 70433, USA;(2) Center for Gene Therapy, School of Medicine, Tulane University, New Orleans, LA, USA;(3) Division of Gene Therapy, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA, USA; |
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Abstract: | Recently, the genetic modification of mesenchymal stem cells (MSCs) has led to increased differentiation potential. For the
therapeutic application of genetically modified MSCs, it is crucial to evaluate their characteristics and safety. In this
study, we investigated the effects of bone morphogenetic protein 2 (BMP2) gene transfer on the characteristics and biodistribution
of human MSCs. Lentiviral-mediated BMP2 transduction to MSCs enhanced osteocyte differentiation and decreased adipocyte differentiation.
Although there is no significant difference in cell proliferation capacity, MSCs transduced BMP2 proliferate somewhat higher
than nontransduced or GFP transduced MSCs. No significant changes were observed in surface antigen expression in genetically
modified MSCs. In vivo transplantation of lentiviral-mediated BMP2 gene transferred MSCs to nude mice did not result in tumor formation. To evaluate
the biodistribution of genetically modified cells, MSCs carrying BMP2 were injected into the tail vein of femur fractured
mice. The introduced MSCs were detected in the spleen, testis and fractured femur 28 days post-implantation. These findings
suggest that diverse safety tests for genetically modified MSCs should be considered, particularly when a lentivirus mediated
gene transfer method is used. |
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