To differentiate or not to differentiate: DNA aptamers answer the question
A team of researchers from Shinshu University (Matsumoto, Japan), the National Institute of Advanced Industrial Science and Technology (Tokyo, Japan) and the University of Shizuoka (Japan) have uncovered a time-dependent effect of a DNA aptamer, iSN04, on stem cell differentiation into the cardiac lineage.
Induced pluripotent stem cells (iPSCs), an ethically viable alternative to embryonic stem cells (ESCs), are reprogrammed somatic cells that have been conferred expanded developmental potency and the ability of self-renewal. These fundamental characteristics, alongside immunological compatibility in an autologous form, grant immense potential as advanced therapies.
Currently, the protocols to direct stem cell fate consist of complicated and expensive combinations of materials, such as transcription factors and growth factors. This hinders the ability to efficiently manipulate iPSCs for clinical therapies, which the researchers set out to address.
The team investigated DNA aptamers, which are small single-stranded DNA molecules that bind target proteins and modulate signaling cascades that are essential in cell fate determination. These molecules make for promising prospects as they are easily modifiable, suitable for long-term storage and can be synthesized economically.
Stem cell-based therapy repairs damaged heart
A stem cell-based therapy has been shown to promote regeneration in damaged cells, offering hope to patients with heart failure.
In previous research, the group showed that the anti-nucleolin DNA aptamer, iSN04, promoted the differentiation of myogenic precursor cells into skeletal muscle cells and also enhanced the differentiation of pluripotent stem cells. Based on this, the team sought to investigate the effect of iSN04 on murine ESCs and iPSCs. This was achieved using a number of assays, including RNA sequencing, cell imaging and molecular interaction and pathway analysis.
The researchers report that iSN04 inhibited the proliferation of undifferentiated ESCs and iPSCs. Concerning ESCs and iPSCs that were actively undergoing differentiation into cardiac cells, the researchers report a time-dependent effect of iSN04, whereby myocardial differentiation into cardiomyocytes was enhanced after 5 days.
This research is the first report of the generation of cardiomyocytes from pluripotent stem cells using DNA aptamers. Expanding the repertoire of tools that control stem cell fate outside the current suite of expensive and complex combinations of transcription factors and other cell culture components is important for increasing the efficiency of advanced therapies production.
Tomohide Takaya, research group leader, concluded: “We believe there is a strong case to be made for further studies evaluating DNA aptamers in regenerative medicine. Aptamers are cost-effective and open up the possibility of producing specific cells from the patient’s stem cells. But it doesn’t end there! Since the aptamers can regulate stem cell fate, they can serve as therapeutic agents for many conditions linked to stem cell dysfunction.”