research shows mature cells can be reprogrammed into re-deployable stem cells
without direct genetic modification. Can usher in a new generation of stem cell
technologies for tissue engineering and regenerative medicine.
The National University of Singapore announced
that it has had a breakthrough in its research into stem cell technology,
tissue engineering, and regenerative
medicine. Recent research led by Professor G.V. Shivashankar of the
Mechanobiology Institute (MBI) at the National University of Singapore (NUS)
and the FIRC Institute of Molecular Oncology (IFOM) in Italy, has revealed that
mature cells can be reprogrammed into re-deployable stem cells without direct
genetic modification – by confining them to a defined geometric space for an
extended period of time.
findings will usher in a new generation of stem cell technologies for tissue
engineering and regenerative medicine that may overcome the negative
effects of geonomic manipulation,” Prof
It was over a decade that scientists first
showed that mature cells can be reprogrammed in the lab to become pluripotent
stem cells that are capable of being developed into any cell type in the body.
In those early studies, researchers genetically modified mature cells by
introducing external factors that reset the genomic programmes of the cells,
essentially turning back the clock and returning them to an undifferentiated or
unspecialised state. The resultant
lab-made cells, known as induced pluripotent stem cells (iPSCs) can then be
programmed into different cell types for use in tissue repair, drug discovery
and even to grow new organs for transplant. Importantly, these cells did not
need to be harvested from embryos.
However, a major obstacle is the tendency
for any specialised cell that is
developed from iPSCs to form tumours
after being introduced into the body. To better understand why and how this
occurred, researchers turned their focus to understanding how stem cell
differentiation and growth is regulated in the body, and in particular, how
cells naturally revert to an immature stem cell-like state or convert to another cell type, during development, or in
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.
cell technologies redefined
The physical parameters used in the study
are reflective of the transient geometric constraints that cells can be exposed
to in the body. For example, during development, the establishment of geometric
patterns and niches are essential in the formation of functional tissues and
organs. Similarly, when tissue is damaged, either through injury or disease,
cells will experience sudden alterations to their environment. In each case,
mature cells may revert back to a pluripotent, stem cell-like state, before
being redeployed as specialised cells for
the repair or maintenance of the tissue.
“While it is well established that
confining stem cells to defined geometric patterns and substrate properties can
direct their differentiation into specialised
cells, this study shows for the first time that mechanical cues can reset the
genomic programmes of mature cells and return them to a pluripotent state,”
Prof Shivashankar explained.
He added, “The use of geometric constraints
to reprogramme mature cells may better reflect the process occurring naturally
within the body. More importantly, our findings allow researchers to generate
stem cells from mature cells with high efficiency and without genetically
The team’s research findings were published
in the Proceedings of the National
Academy of Sciences of the United States of America (PNAS) in May
2018. PNAS is one of the world's most-cited and comprehensive multidisciplinary
scientific journals, publishing more than 3,200 research papers annually.
Professor G.V. Shivashankar and his team’s
findings herald a significant breakthrough in stem cell technology and will
enable the delivery of more efficient and effective healthcare.
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