Shuttle of lentiviral vectors via transplanted cells in vivo

• Published in: Gene therapy Vol. 12; no. 1; pp. 67 - 74
• Main Authors: BLÖMER, U, GRUH, I, WITSCHEL, H, HAVERICH, A, MARTIN, U
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 2005
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Cell Line; Cell Transplantation; Fibroblasts - virology; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic Therapy - adverse effects; Genetic Therapy - methods; Genetic vectors; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Health aspects; Health. Pharmaceutical industry; Humans; Immunohistochemistry; Industrial applications and implications. Economical aspects; Lentivirus - genetics; Lentivirus Infections - transmission; Medical sciences; Methods; Myocytes, Cardiac - virology; Physiological aspects; Rats; Rats, Wistar; Stem cells; Transduction, Genetic - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Germany; Virus; In vivo; cell transplantation; gene transfer; Retroviridae; Shuttle vector; Transplantation; Gene therapy; Lentivirus; lentiviral vector; Genetic transfer
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302384

Lentiviral vectors have turned out to be an efficient method for stable gene transfer in vitro and in vivo. Not only do fields of application include cell marking and tracing following transplantation in vivo, but also the stable delivery of biological active proteins for gene therapy. A variety of cells, however, need immediate transplantation after preparation, for example, to prevent cell death, differentiation or de-differentiation. Although these cells are usually washed several times following lentiviral transduction, there may be the risk of viral vector shuttle via transplanted cells resulting in undesired in vivo transduction of recipient cells. We investigated whether infectious lentiviral particles are transmitted via ex vivo lentivirally transduced cells. To this end, we explored potential viral shuttle via ex vivo lentivirally transduced cardiomyocytes in vitro and following transplantation into the brain and peripheral muscle. We demonstrate that, even after extensive washing, infectious viral vector particles can be detected in cell suspensions. Those lentiviral vector particles were able to transduce target cells in transwell experiments. Moreover, transmitted vector particles stably transduced resident cells of the recipient central nervous system and muscle in vivo. Our results of lentiviral vector shuttle via transduced cardiomyocytes are significant for both ex vivo gene therapy and for lentiviral cell tracing, in particular for investigation of stem cell differentiation in transplantation models and co-cultivation systems.