Delivery of Therapeutic Molecules by Transplantation of Genome-Edited Induced Pluripotent Stem Cells
| Autor: | Ittetsu Nakajima, Takahiro Tsukimura, Terumi Ono, Tomoko Shiga, Hiroshi Shitara, Tadayasu Togawa, Hitoshi Sakuraba, Yuichiro Miyaoka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Cell Transplantation, Vol 32 (2023) |
| Druh dokumentu: | article |
| ISSN: | 1555-3892 09636897 |
| DOI: | 10.1177/09636897231173734 |
| Popis: | Human induced pluripotent stem cells (iPSCs) have already been used in transplantation therapies. Currently, cells from healthy people are transplanted into patients with diseases. With the rapid evolution of genome editing technology, genetic modification could be applied to enhance the therapeutic effects of iPSCs, such as the introduction of secreted molecules to make the cells a drug delivery system. Here, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the lack of α-galactosidase A (GLA). We previously developed an immunotolerant therapeutic molecule, modified α- N -acetylgalactosaminidase (mNAGA). We confirmed that secreted mNAGA from genome-edited iPSCs compensated for the GLA activity in GLA-deficient cells using an in vitro co-culture system. Moreover, iPSCs transplanted into Fabry model mice secreted mNAGA and supplied GLA activity to the liver. This study demonstrates the great potential of genome-edited iPSCs secreting therapeutic molecules. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|