| RRC ID |
55895
|
| Author |
Ide K, Mitsui K, Irie R, Matsushita Y, Ijichi N, Toyodome S, Kosai KI.
|
| Title |
A Novel Construction of Lentiviral Vectors for Eliminating Tumorigenic Cells from Pluripotent Stem Cells.
|
| Journal |
Stem Cells
|
| Abstract |
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 (SGs) 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 SGs. Our two-plasmid system achieved rapid and simultaneous construction of different TC-LVs with different promoters. Ganciclovir (GCV) exerted remarkable cytotoxicity in herpes simplex virus thymidine kinase-transduced hPSCs, and high specificity for undifferentiated cells was achieved using the survivin promoter (TC-LV.Surv). Moreover, GCV 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 SG for specific and complete elimination of tumorigenic hPSCs, facilitating the development of safe regenerative medicine. Stem Cells 2018;36:230-239.
|
| Volume |
36(2)
|
| Pages |
230-239
|
| Published |
2018-2-1
|
| DOI |
10.1002/stem.2725
|
| PMID |
29067732
|
| MeSH |
Animals
Cell Line
Female
Ganciclovir / therapeutic use*
Genetic Vectors / genetics*
Humans
Lentivirus / genetics*
Mice
Pluripotent Stem Cells / cytology*
Pluripotent Stem Cells / metabolism*
Promoter Regions, Genetic / genetics
Simplexvirus / genetics
Teratoma / drug therapy
Thymidine Kinase / genetics
|
| IF |
5.614
|
| Times Cited |
2
|
| Resource |
| Human and Animal Cells |
201B7(HPS0063) |
