A Novel Construction of Lentiviral Vectors for Eliminating Tumorigenic Cells from Pluripotent Stem Cells
| Autor: | Soichiro Toyodome, Rie Irie, Kaoru Mitsui, Ken-ichiro Kosai, Yohei Matsushita, Nobuhiro Ijichi, Kanako Ide |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pluripotent Stem Cells Transgene Genetic enhancement Genetic Vectors Biology Regenerative medicine Thymidine Kinase Viral vector Cell Line 03 medical and health sciences Mice Animals Humans Simplexvirus Induced pluripotent stem cell Promoter Regions Genetic Ganciclovir Lentivirus Teratoma Cell Biology Suicide gene Molecular biology Transplantation 030104 developmental biology Cancer research Molecular Medicine Female Stem cell Developmental Biology |
| Zdroj: | Stem cells (Dayton, Ohio). 36(2) |
| ISSN: | 1549-4918 |
| Popis: | The risk of tumor formation poses a challenge for human pluripotent stem cell (hPSC)-based transplantation therapy. Specific and total elimination of tumorigenic hPSCs by suicide genes has not been achieved because no methodology currently exists for testing multiple candidate transgene constructs. Here, we present a novel method for efficient generation of tumorigenic cell-targeting lentiviral vectors (TC-LVs) with diverse promoters upstream of a fluorescent protein and suicide genes. Our two-plasmid system achieved rapid and simultaneous construction of different TC-LVs with different promoters. Ganciclovir exerted remarkable cytotoxicity in herpes simplex virus thymidine kinase (HSV-tk)-transduced hPSCs, and high specificity for undifferentiated cells was achieved using the survivin promoter (TC-LV.Surv). Moreover, ganciclovir treatment completely abolished teratoma formation by TC-LV.Surv-infected hPSCs transplanted into mice, without harmful effects. Thus, TC-LV can efficiently identify the best promoter and suicide gene for specific and complete elimination of tumorigenic hPSCs, facilitating the development of safe regenerative medicine. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text