Prof Shivashankar’s team of researchers has shown that mature cells can be reprogrammed, in vitro, into pluripotent stem cells without genetically modifying the mature cells, simply by confining the cells to a defined area for growth.
Resetting mature cells
When fibroblast cells (a type of mature cell found in connective tissue such as tendons and ligaments) were confined to rectangular areas, they quickly assumed the shape of the substrate (the surface or medium that the cells are attached to). Based on previous work from the Shivashankar lab, this indicated that the cells were measuring and responding to the physical properties of their environment, and conveying this information to the nucleus where DNA packaging and genome programmes would adapt accordingly.
The team grew the cells over 10 days until they formed spherical clusters of cells. Genetic analysis of the cells within these clusters revealed that specific characteristics of chromatin (the condensed form of packaged DNA) normally associated with mature fibroblasts were lost by the sixth day. By the 10th day, the cells expressed genes normally associated with embryonic stem cells and iPSCs. The researchers have now learnt that by confining the mature cells for an extended period of time, mature fibroblasts can be turned into pluripotent stem cells.
To confirm that the fibroblasts had indeed been reprogrammed into stem cells, the researchers then directed their growth, with high efficiency, into two different specialised cell types. Some cells were also directed back into fibroblasts.
Stem cell technologies redefined