Achieving a controlled and reproducible means to direct stem cell differentiation is the single most critical concern scientists have been trying to address since the discovery of stem cells. In this regard, the use of small molecules and RNA interference offers unique advantages by targeting different cellular mechanisms. However, a majority of small molecules tend to be very hydrophobic and lack solubility in physiological solutions, which can greatly impair its delivery and efficacy. Similarly, delivering negatively-charged siRNA into stem cells while maintaining high cellular viability has proven to be a major challenge.
Addressing this challenge, scientists from Prof. KiBum Lee’s Lab (Shreyas Shah, Aniruddh Solanki and Piyush Sasmal) have synthesized a multifunctional vehicle comprised of a cyclodextrin-modified dendritic polyamine construct (termed DexAM). DexAM was used to complex the negatively-charged siRNA (through electrostatic interactions) and encapsulate the small molecule (within the cyclodextrin cavity) within a single vehicle. This DexAM complex was then used for the simultaneous delivery of small molecules and siRNA into neural stem cells to achieve enhanced neuronal differentiation. With the increasing interest in achieving precise control over stem cell differentiation, such a platform can serve as a step towards bridging the gap between basic science and clinically-relevant treatments.
This work was recently published in JACS (Shah, S. et al. 2013, 135(42): 15682–15685) and highlighted in SciBX (Science-Business eXchange journal from Nature Publishing Group).
More Information: http://pubs.acs.org/doi/abs/10.1021/ja4071738
Prof. KiBum Lee
Year of Research Highlight: 2013