SCIENTISTS CREATE THERAPY GRADE STEM CELLS CAUSING NEW COCKTAIL TO REPROGRAM ADULT CELLS
Researchers at the
Hebrew University of Jerusalem have developed a new cocktail that is highly
effective at coaxing adult cells to become quality pluripotent stem cells
Regenerative medicine
is a new and expanding area that aims to replace lost or damaged cells, tissues
or organs through cellular transplantation. Because stem cells derived from
human embryos can trigger ethical concerns, a good solution is reprogramming
adult cells back to an embryo-like state using a combination of reprogramming
factors.
The resulting cells,
called induced pluripotent stem cells (iPSCs), could be used to replace those
lost to damage or disease. However, scientists have discovered that the process
of reprogramming adult cells can introduce genetic abnormalities that limit the
cells' usefulness in research and medicine.
To make iPSCs,
scientists expose adult cells to a cocktail of genes that are active in
embryonic stem cells. iPSCs can then be coaxed to differentiate into other cell
types such as nerve or muscle. However, the standard combination of factors
used to reprogram cells leads to a high percentage of serious genomic
aberrations in the resulting cells. (The reprogramming factors are Oct4, Sox2,
Klf4, and Myc -- known collectively as OSKM).
Now researchers at the
Hebrew University of Jerusalem have developed a new cocktail of reprogramming
factors that produce high-quality iPSCs. Dr. Yosef Buganim, at the Institute
for Medical Research Israel-Canada in the Hebrew University's Faculty of
Medicine, worked with scientists at the lab of Whitehead Institute founding
member Rudolf Jaenisch, a professor of biology at MIT.
The researchers
reasoned that changing the reprogramming factors could reprogram the adult
cells in a more controlled way and yield high-quality iPSCs. Working with mouse
cells, Dr. Buganim and research scientist Styliani Markoulaki used
bioinformatic analysis to design a new cocktail of reprogramming factors
(Sall4, Nanog, Esrrb, and Lin28, known collectively as SNEL).
Their results showed
that the interaction between reprogramming factors plays a crucial role in
determining the quantity and quality of resulting iPSCs -- and that a different
combination of reprogramming factors can in fact produce a much higher quality
product.
The new SNEL cocktail
created fewer colonies of iPSCs, but approximately 80% of those produced passed
the most stringent pluripotency test. This is highly preferable to the
traditional OSKM cocktail, which produces a large number of colonies but the
majority of which fail the pluripotency test.
Dr. Buganim
hypothesizes that SNEL may reprogram cells better than OSKM because it does not
rely on the master regulators Oct4 and Sox2, which might activate part of the
adult cell genome. According to Buganim, the research demonstrates the
effectiveness of bioinformatics tools in producing high quality iPSCs.
This study takes the
regenerative medicine field one step closer to the clinic, where it may be able
to help patients in need of cellular transplantation therapy. The researchers
will now seek to define the optimal combinations for reprogramming human iPSCs,
which are harder to reprogram than mouse cells and which could not be
reprogrammed using the SNEL cocktail.
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