National University of Singapore’s breakthrough findings signal a new generation of stem cell tech 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.
“Our breakthrough 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 Shivashankar stated.
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 tissue maintenance.
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.
Stem 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 modifying them.”
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.