Abstract
Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 5336-5343 |
| Number of pages | 8 |
| Journal | Biomaterials |
| Volume | 34 |
| Issue number | 21 |
| DOIs | |
| State | Published - Jul 2013 |
| Externally published | Yes |
Bibliographical note
Funding Information:We would like to thank members of A.C.A.W. and Y.Y.Y. labs for their technical assistance and helpful discussions. Authors would like to thank Dr Steve Oh (Bioprocessing Technology Institute, Singapore) for the generous gift of iPSCs developed using viral vectors. Funding was provided by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore).
Keywords
- Cationic bolaamphiphile
- Induced pluripotent stem cells
- Intracellular delivery
- Protein transduction
- Reprogramming of fibroblasts
- Stem cells
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Ceramics and Composites
- Biomaterials
- Mechanics of Materials