Gene delivery to stem cells holds great potential for tissue regeneration and delivery of therapeutic proteins. The major barrier is the lack of safe and efficient delivery methods. Here, we report enhanced gene delivery systems for human stem cells using biodegradable polymeric vectors. A library of poly (β-amino esters) end-modified derivatives was developed and optimized for high transfection efficiency and low cytotoxicity for three human stem cell lines including human mesenchymal stem cells (hMSCs), human adipose-derived stem cells (hADSCs) and human embryonic stem cell-derived cells (hESCds). In the presence of 10% serum, leading end-modified C32 polymeric vectors exhibited significantly high transfection efficiency in hMSCs (27±2%), hADSCs (24±3%) and hESCds (56±11%), with high cell viability (87-97%) achieved in all cell types. Our results show that poly(β-amino esters) as a class, and end-modified versions of C32 in particular, are efficient polymeric vectors for gene delivery to both adult and embryonic-derived stem cells.
Bibliographical noteFunding Information:
We thank the NIH (R01-EB000244-27 and R01-DE016516-03) for funding. FY gratefully acknowledge the National Institutes of Health for National Research Service Award postdoctoral fellowship (1F32 AR056567-01). We also thank the laboratory of Professor Johnny Huard at the University of Pittsburgh for kindly providing us the DNA plasmid-encoding human vascular endothelial growth factor 165 used in this study.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology