New technologies derived from stem cell research have found
applications in many areas, such as cosmetic surgery, cancer treatment, and
organ transplantation. Prof Ren-He Xu, from the Faculty of Health Sciences,
University of Macau (UM), has devoted himself to stem cell research for nearly
20 years, hoping to find a new way to treat disease.
Arousing the Interest
of the Father of Human Pluripotent Stem Cells
Xu received his bachelor’s and master’s degrees
in medical sciences from South China University and Central South University, respectively.
Later, he obtained a doctoral degree from the University of Tokyo, Japan, and received
postdoctoral training at both Bar-Ilan University, Israel, and the National Institutes
of Health (NIH), United States.
In 1999, he quit his job at the NIH and began to contemplate
the future direction of his research. Then he stumbled upon an internet article
about stem cell research, which was the hottest subject in medicine at the
time. He summoned up his courage
and sent his personal resume to Prof James Thomson, known as the father of
human embryonic stem cells. Twenty minutes later, he received a phone call from
Prof Thomson, who expressed a strong interest in his research and invited him
to work at WiCell Research Institute at the University of Wisconsin-Madison. ‘I
feel very honoured that an eminent scientist like James Thomson invited me to
work with him,’ recalls Prof Xu. He immediately
accepted the invitation and became the first senior scientist at the institute,
thus beginning his research on stem cells.
Helping Patients with
The journey of stem cell research is an arduous, bittersweet
one, but Prof Xu enjoys the process. ‘In the past, I was mainly focused on
the biology and molecular mechanism of stem cells. But with my medical
training, I kept thinking how I could use my expertise to help patients and ordinary
people,’ he says. ‘If I just study the biology and molecular
mechanism of stem cells, it would be very difficult for me to achieve that goal,
so I decided to study how stem cells can be used to treat diseases.’
In Prof Xu’s opinion, those with medical training
do not necessarily have to become doctors to help people. Becoming a researcher
is another option.
In 2014, he began to develop mesenchymal stem cells (MSC).
Some have likened MSC to the Monkey King [a mythological figure that features
in a body of Chinese legends who can transform into different animals and
objects], because MSC can generate different types of cells. Some say MSC are
like a medicinal balm, because they provide a low-risk treatment for many
diseases. Prof Xu was the first to derive MSC from human embryonic stem cells (hESC) via trophoblast-like
cells. MSC show significant results in treating multiple sclerosis and inflammatory
Over the years, Prof Xu has achieved numerous breakthroughs
in stem cell research, which has earned him recognition from the scientific community.
For example, he discovered an extraneous agent that enables self-regeneration and
long-term in-vitro culture of hESC without having to rely on mouse embryonic fibroblast-conditioned
medium. With this extraneous agent, experiments on hESC can be conducted under
precise conditions to achieve more accurate results, as using animal embryonic
fibroblast-conditioned medium can affect clinical applications of stem cells.
Prof Xu has published nearly 60 papers on stem cell research,
some of which are in leading scientific journals, including Biomaterials , Nature
Methods , Nature Biotechnology , Cell Stem Cell , PNAS , and Stem Cell Reports .
He also holds several patents.
An Accidental Breakthrough
Stem cells require precise culture conditions and careful nurturing.
They need to be frozen before long-distance transport, which can cost hundreds,
sometimes even thousands of, US dollars. Moreover, airlines have regulations concerning
the manner in which stem cells can be carried onto a plane. A small amount of cells
can be stored in culture tubes. However, exposure to ambient conditions for
more than 48 hours will cause the cells to quickly lose their functions and
In 2015, one of Prof Xu’s students conducted an
experiment. He prepared stem cells to form spheroids and then studied their
properties under 3D condition. After the experiment was over, he left the test
tube that contained the cells in the laboratory. One week later, he went back to
check the test tube, expecting to see only dead cells. But what he found
astonished him. The cells in the tube were still alive, without showing any
signs of dying.
After learning the outcome of the experiment, Prof Xu
immediately decided to investigate. He found that the viability of spheroids
formed of stem cells remained above 90 percent even after 11 days. Using an
analogy to illustrate this phenomenon, he says: ‘Stem
cells forming spheroids is like animals entering hibernation in winter. Normally,
cells are incubated at 37 degrees Celsius, but when placed on the table, the
temperature drops to room temperature, around 25 degrees. At this temperature, spheroidal
formation protects the cells via reduction of metabolic rates and conservation of
This discovery eliminates the need to freeze cells before
long-distance transport. With this new UM-developed technology, called spheropreservation,
stem cells which aggregate can be transported at room temperature to almost
anywhere in the world for scientific research or clinical treatment at a cost
of merely several US dollars.
Comparable to US in
Having worked in the US for 20 years, Prof Xu has received
numerous awards for his achievements in stem cell research. These include the
Royan International Research Award
from Royan Institute, the CURE Award for Excellence in Stem Cell Research from
the Connecticut United for Research Excellence (CURE), the Honoree of 2007
Annual State Bluebook of Connecticut, issued by the state secretary, and the
Scientific Achievement Award from the Frederick Research Center of the US
2012, Prof Xu, who was then an associate professor at the University of Connecticut
and the director of the university’s Stem Cell Institute, met Prof
Chuxia Deng from the NIH at a conference they both attended. Prof Deng had just
been appointed dean of the new Faculty of Health Sciences (FHS) at UM, and
eager to recruit new blood for the fledgling faculty, Prof Deng immediately
invited Prof Xu to join UM.
research relies heavily on government support, both financially and
policy-wise,’ says Prof Xu. ‘In terms of research facilities and funding,
UM is comparable to universities in the US and many other places. Moreover, the
Country, Two Systems” policy gives Macao an added advantage.
These are all important reasons that drew me to UM.’
Prof Xu and his team are deepening their stem cell research. They hope to
improve the safety of hESC-derived therapies and minimise immune response
through genome editing, in order to develop hESC-derived MSC into drugs and
provide suitable stem cell treatment for patients National Cancer Institute.