Weizmann Institute scientists have streamlined the painstaking process of
turning the clock back on adult cells in the human body and changing them into
embryonic-like stem cells to replace sick cells, according to a study just
published in the prestigious journal Nature.
Embryonic stem cells have
the potential to treat and cure many medical problems.
That is why the
discovery that induced-embryonic-like stem cells can be created from skin cells
(iPS cells) was rewarded with a Nobel Prize in 2012.
Scientists have been
removing one protein from adult cells to turn them into a stem-cell-like state.
But the process has remained frustratingly slow and inefficient, and the
resulting stem cells are not yet ready for medical use.
The new research
in the Rehovot lab of Dr. Yaqub Hanna dramatically changes that. He and his
colleagues revealed the “brakes” holding back the production of stem cells and
found that releasing this brake can synchronize the process and increase its
efficiency from around 1 percent or less today to 100%.
They say their
findings may help facilitate the production of stem cells for medical use, as
well as advance our understanding of the mysterious process by which adult cells
can revert back into their original, embryonic state.
cells are those that have not undergone any “specialization” so they can give
rise to any type of cell in the body. This is what makes them so
They can be used, among other things, to repair damaged tissue,
treat autoimmune disease and even grow transplant organs.
cells taken from embryos is difficult because of there are not large supplies
and because of ethical concerns (although Jewish law is liberal on using
unimplanted embryos for medical research that would benefit mankind, so Israeli
researchers do not face the limitations in other countries).
for their use were renewed in 2006, when a team led by Shinya Yamanaka of Kyoto
University discovered it is possible to “reprogram” adult cells.
resulting cells, called “induced pluripotent stem cells (iPSCs), are created by
inserting four genes into their DNA. Despite this breakthrough, the reprograming
process is very difficult: It can take up to a month; the timing is not
coordinated among the cells; and less than 1% of the treated cells end up
becoming stem cells.
Hanna and his team wondered what the main obstacle
was that prevents successful reprograming in the majority of cells. In his
postdoctoral research, Hanna had employed mathematical models to show that a
single obstacle was responsible. Of course in biology, Hanna is the first to
admit, experimental proof is required to back up the models. The present study
not only provides the proof, it identifies that single obstacle and shows that
removing it can dramatically improve reprograming.
Hanna’s group, led by
Dr. Noa Novershtern, Yoach Rais, Asaf Zviran and Shay Geula of the
molecular genetics department, together with members of the genomics unit of the
Weizmann Institute’s Israel Structural Proteomics Center, studied a protein
called MBD3, whose function was unknown. MBD3 had caught their attention because
– unusually – it is expressed in every cell in the body, at every stage of
Most proteins are produced in specific cells, at specific
times, for specific functions.
The team found that there is one exception
to the rule of universal expression of this protein – the first three days after
conception. These are exactly the three days in which the fertilized egg begins
dividing, and the nascent embryo is a growing ball of pluripotent stem cells
that will eventually supply all the cell types in the body.
the fourth day, differentiation begins and the cells start to lose their
pluripotent status. And that is just when the MBD3 proteins first
This finding has significant implications for the producing iPSCs
for medical use. Yamanaka used viruses to insert the four genes but, for safety
reasons, these are not used in reprograming cells to be used in
This gives the process an even lower success rate of only
around a 10th of a percent.
The Weizmann researchers showed that removing
MBD3 from the adult cells can improve efficiency and speed the process by orders
of magnitude. The time needed to produce the stem cells was shortened from four
weeks to eight days. As a bonus, since the cells all underwent the reprograming
at the same rate, the scientists will now be able, for the first time, to follow
it step by step and reveal its mechanisms of operation.
Hanna points out
that his team’s achievement was based on research into the natural pathways of
embryonic development. Scientists investigating reprograming, he concludes, can
benefit from a deeper understanding of how embryonic stem cells are produced in
“After all, nature still makes them best, in the most efficient