Journal
GENE THERAPY
Volume 16, Issue 4, Pages 533-546Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2008.182
Keywords
stem cells; gene delivery; biodegradable; polymeric vectors
Categories
Funding
- NIH [R01-EB000244-27, R01-DE01651603]
- National Institutes of Health for National Research Service [1F32 AR056567-01]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [F32AR056567] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB000244, R37EB000244] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE016516] Funding Source: NIH RePORTER
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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 (beta- 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(beta-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.
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