STEM CELLS NEWS UPDATE: A PERSONAL PERSPECTIVE
Wong SC
*Corresponding Author: Shiu C. Wong, Ph.D., M.B.A., Stem Cell Link, Hong Lok Building, Block M, 1st
Floor, 96 Chik Fuk Street, Tai Wai, New Territories, Hong Kong, Special Administration Region, People’s Republic
of China; Tel.: +852-677-22933; E-mail: scwong555@gmail.com
page: 7
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INTRODUCTION
This article is a follow-up to my Commentary
published in this Journal 2 years ago [1], and
is dedicated to the memory of Professor Dr. Georgi
D. Efremov (founder and first Editor-in-Chief
of BJMG) and Professor Dr. Titus H.J. Huisman
(founder and first Editor-in-Chief of Hemoglobin).
It will put closure to some of the events mentioned
in the previous Commentary, and then continue with
news and websites concerning some of the recent
developments in the emerging field of Regenerative
Medicine.
What Has Happened Since 2011. In my 2011
Commentary, I quoted the ‘parallel’ between IVF
(in vitro ferti-lization) and stem cells, and cited the
award of the 2010 Nobel Prize for Medicine to Professor
Robert Geoffrey Edwards for his pioneering
work in human IVF. There are two updates. First
and sadly, it is heart-breaking to report that Professor
Edwards died on Wednesday, April 10 2013, at
the age of 87 [2]. Second, on a happier note, for
their work on stem cells and the discovery of iPSC
(induced pluripotent stem cells), Professor John
B. Gurdon and Professor Shinya Yamanaka were
awarded the 2012 Nobel Prize for Medicine [3].
For the past decade, the continuing argument
on the legality of US Federal funding for human
embryonic stem cells (hESC) research as well as
the court petition Sherley vs. Sebelius (12-454) [viz.
James L. Sherley and Theresa Deisher (two stem
cell scientists) vs. Kathleen Sebelius (Secretary, Department
of Health & Human Services, NIH)] came
to a closure earlier this year. On January 10 2013,
the US Supreme Court, to the delight of many, put
an end to this legal ‘saga’ once for all, by refusing
to hear the case [4].
In the meantime, there have been bad news and
good news concerning the first two Food and Drug
Administration (FDA)-approved clinical trials. First the bad news: on November 4 2011, the Californiabased
Geron’s clinical trial of a hESC-based therapy
for spinal cord injury was halted citing financial reasons.
Luckily, earlier this year (on January 7 2013),
the California-based BioTime announced that they
would buy all Geron’s hESC assets [5]. I look forward
to better news from BioTime.
Unlike Geron, the Advanced Cell Technology
(ACT) macular dystrophy project has nothing but
good news. A preliminary January 23 2012 report
in Lancet [6] described improved vision of two
California women, 4 months after the injection of
50,000 of hESC-derived retinal pigment epithelial
(RPE) cells under the retina. Since then, most of the
other 22 similarly treated patients also had improvements
in vision. I cannot wait for more good news
from ACT.
Besides the Geron and ACT clinical trials, the
first UK phase I clinical trial of a neural stem cell
therapy using ReNeuron’s ReN001 for stroke patients
also had good news, viz. mild to moderate improvements
were observed in five of the nine longterm
stroke patients [7]. Thus, the PISCES trial in
the UK looks promising as well.
Regarding the ‘law enforcement’ story, first
broadcast in April 2010 in the American television
program “60 Minutes” and included in my 2011
Commentary [1], there should be closure soon. In
January 2012, the FBI (Federal Bureau of Investigation)
arrested three of the individuals who preyed
on the sick with ‘miracle stem cell cure’, and was
going after the fourth man [8]. In the meantime, the
crackdown on this kind of unscrupulous individuals
continues. For example, a Bonita Springs cardiologist,
Zannos Grekos, has recently been (March
2013) prosecuted for “unorthodox stem cell therapy
in 2010 on 69-year-old Domenica Fitzgerald” who
died on April 4, 2010 [9].
The above section of this article updates some
of the events that have been referred to in my 2011
Commentary [1]. The following sections will highlight
more recent news on stem cells. I will start with
two pieces of ‘news with a twist’: 1) the 2012 Nobel
Prize, and 2) the May 2013 article in Cell on the
successful cloning of human embryonic stem cells.
The 2012 Nobel Prize and the Lawsuit. Only
a few months after the award of the 2012 Nobel
Prize for Medicine to John B. Gurdon and Shinya
Yamanaka, a California surgeon Rongxiang Xu
filed a lawsuit “suing the Nobel Assembly for failing
to recognize him for his work on regenerative
medicine,” and a separate lawsuit against both the
Nobel Laureates [10,11].
It is surely sad to read such news, especially as
it involves a lawsuit, the first of its kind, against the
Medical Nobel Assembly at the Karolinska Institute
in Sweden. However, it reminds me of a similar lament
by Bruno Lemaitre towards Jules Hoffman
(one of the 2011 Nobel Prize winners) on Lemaitre’s
contribution to the discovery of the “Toll and
Imd pathways in Drosophila immunity” [12]. After
Lemaitre’s lament, a satiric question was raised: “A
Nobel Prize not Immune from Error?” [13].
Article Regarding Nuclear Transfer-Human
Embryonic Stem Cells/“A New Kind of
Stem Cell”. Cell published the cloning of human
embryonic stem cells by Dr. Shoukhrat Mitalipov
(Tachibana et al., [14]) in Portland, OR, USA using
the technique of somatic cell nuclear transfer
(SCNT) previously used for the cloning of Dolly
The Sheep in 1996. The newly discovered NThESC
(nuclear transfer-human embryonic stem
cell) was immediately hailed as the “new stem cells
on the block” and as “a tour de force and an unparalleled
achievement”. However, only a few days after
its publication, these findings were over-shadowed
by an anonymous comment in Pubpeer. com questioning
problems in the paper [15]. A follow-up in
Nature News by Cyranoski [16] reported that Dr.
Shoukhrat Mitalipov indeed acknowledged errors in
his paper, but insisted that “The results are real, the
cell lines are real, everything is real.”
Personally, I hope that the errors in the Tachibana
et al. [14] article could be amended and the scientific
findings confirmed as soon as possible. I
surely hope that, in the near future, I do not have to
read any more follow-up news on the NT-hESC story
similar to the news on the “Rise and Fall” of Woo
Suk Hwang, the Korean stem cell researcher [17].
Searching for Truly Pluripotent Adult Stem
Cells. Having mentioned Dr. Yamanaka’s iPSC and
Dr. Tachi-bana’s NT-eESC above, I would like to
report briefly three recent findings on the search for
sources of the truly pluripotent adult stem cells, viz.
1) kidney cells in urine, 2) breast tissue and 3) adipose
tissue. First, regarding urine as a source, it was
Dr. Duangqing Pei’s team of researchers in Guangzhou,
People’s Republic of China (PRC) [Zhou et al.,18] who in 2011, reported the successful reprogramming
of kidney epithelial cells harvested from urine
into human iPSCs that could then turn into neural
progenitor cells. Commenting on urine being a possible
source for pluripotent adult stem cells, Dr. Marc
Lelande, a geneticist at the University of Connecticut
Health Center, said: “We work on childhood disorders,
and it’s easier to get a child to give a urine sample
than to prick them for blood.” Very true indeed!
Second, regarding breast tissues as a source,
it was Dr. Thea Tlsty of University of California,
San Francisco (UCSF), CA, USA, who in 2013, reported
her discovery of a rare population of stem
cells collected from human breast tissue of healthy
adults. She named these adult stem cells ‘endogenous
pluripotent stem cells’ (ePSC) that could be reprogrammed
to beating heart cells [Roy et al., 19].
Third, regarding adipose tissue as a source, it
was Dr. Gregorio Chazenbalk who in 2013, reported
the discovery of ‘Muse-AT cells’, i.e., multilineagedifferentiating
stress-enduring cells, derived from
adipose tissue [Heneidi et al., 20]. These Muse-AT
cells were able to differentiate into mesenchymal,
endodermal and ectodermal cells, viz. adipocytes,
hepatocytes and neural cells. The finding of ‘truly
pluripotent adult stem cells’ from body fat, easily
obtainable via liposuction, was hailed as “something
of a holy grail for an abundant, cheap and
easy-to-obtain source of stem cells.”PAGE
The above-described three potential sources
of truly pluripotent adult stem cells, if proven to
be the case, will surely be important assets in the
practice of Regenerative Medicine. I cannot wait to
hear more positive results from Guangzhou, PRC,
San Francisco and Los Angeles, CA, USA. On a
lighter note, the ‘fat’ story bears a similar ring to the
‘urine’ story, i.e., it may turn out that two possible
ideal sources of truly pluripotent adult stem cells are
two things in our body that, when in excess, we are
happy to get rid of!
Reprogramming In Vivo/Embryonic Stem
Cells Created in Living Mice. The above-described
iPSCs from urine, breast tissue and adipose
tissue are created via in vitro reprogramming of the
adult human cell sources in laboratories. In a recent
article in Nature, Professor Manuel Serrano and Dr.
Maria Abad of Spain reported the recovery of iPSC
via in vivo reprogramming in life animal [Abad et
al., 21]. Induction of embryonic-state stem cells in
bio-engineered mice was successfully carried out
with the insertion of extra copies of Oct4, Sox2,
Klf4 and c-Mycin genes that were then switched
on by feeding the mice with the antibiotic doxycycline.
These iPSCs from in vivo reprogramming
have characteristics of embryonic stem cells and
even have totipotent properties equivalent to those
observed in 16-cell human embryos. I look forward
to hearing news concerning clinical applications of
this in vivo reprogramming protocol, and hope that
regeneration of specific cell types within our own
bodies can soon be achieved to replace damaged organs
in the near future.
Holy Grail of Regenerative Medicine. It is
the general consensus that the ‘Holy Grail’ of stem
cell research is the creation of whole working organs
for transplant. The search for ‘replacement
parts’, viz. whole working organs of a) bladder, b)
heart and c) trachea was chronicled by Yong [22]. In
2006, Professor Anthony Atala and colleagues [23]
of Wake Forest Institute for Regenerative Medicine
(Winston-Salem, NC) successfully implanted seven
patients with auto-logous-engineered bladder constructs
on scaffolds made of a composite of collagen
and polyglycolic acid. It was hailed as ‘a milestone’
in the science of growing organs. Another
‘milestone’ came in 2008, when Dr. Harald Ott of
the Massachusetts General Hospital (Boston, MA),
and Dr. Doris Taylor of the University of Minnesota
(Minneapolis, MN) reported their results of using
decellularized cadaveric rat hearts as scaffolds
for engineering bioarti-ficial hearts [Ott et al., 24].
Three years later, it was reported that Dr. Taylor
succeeded in carrying out ‘whole organ decellularization’
of human cadaveric hearts and reseeding
the ghost hearts, i.e., the scaffolds, with human
adult stem cells to produce regenerated hearts in her
laboratory [25]. Back in the same year of 2008, the
landmark trachea replacement was achieved by pioneering
surgeon Professor Paolo Macchi-arini (Barcelona,
Spain and his professional collaborators
[26], who successfully transplanted the first tissueengineered
trachea to 30-year-old Claudia Castillo
in Barcelona. As of July 2013, Professor Macchiarini
and his colleagues have carried out 15 trachea
operations using the patients’ own stem cells seeded
onto man-made scaffolds or cadaveric scaffolds.
Two of Professor Macchiarini’s 15 trachea-patients
were children, viz. 11-year old Ciaran FinnLynch and 2-year old Hannah Warren. In March
2010, Ciaran Finn-Lynch (born with Long Segment
Tracheal Stenosis) became the first 11-year old boy
whose own body was used as a ‘bioreactor’ (because
of the urgency in this case) where his own
stem cells, seeded on a donated trachea-scaffold,
were allowed to repopulate and grow [27]. Professor
Macchiarini and Professor Martin Birchall
of University College London, London, UK, performed
this ‘historic’ trachea operation at the Great
Ormond Street Hospital for Children in London,
UK. Two years after the operation, Ciaran was 11
cm taller and his windpipe had also grown with him
inside his body. Dr. Harald Ott commented that “the
holy grail of tissue engineering is to come up with
something that is so integrated into the human body
that it grows with the human body.” The story of
Ciaran is certainly amazing.
On the other hand, the story of Hannah Warren,
the youngest-ever ‘trachea transplant’ patient, does
not have such a happy ending. However, her story
is surely an inspirational one. Hannah, a 2-year-old
Korean-Canadian, was born without a trachea (i.e.,
Tracheal Agenesis) and had been kept alive with a
substituted windpipe. Dr. Mark Holterman of the
Children’s Hospital of Illinois in Peoria, IL, USA,
helped to bring Hannah from Korea to the United
States. In April 2013, Professor Macchiarini from
Stockholm led the surgical team in a 9-hour operation
of transplanting an artificial trachea into Hannah
(of a plastic-fiber-scaffold) seeded with her
own bone marrow cells [28]. After this historic
trachea operation, Hannah’s father, Darryl Warren,
exclaimed “We feel like she’s reborn.” However, it
was heart-breaking to learn that 3 months after the
ground-breaking windpipe transplant, Hannah died
on July 6 as a result of “additional health issues.”
The statement by the Children’s Hospital of Illinois
declared that “we take comfort in the knowledge that
the efforts of her physicians and the care team working
with them will benefit and serve other children
and adults in the years to come.” Well said indeed!
Expansion and Rapid Establishment of
Stem Cell Centers Around the World. In the US,
after President Bush’s 2001 executive order limiting
federal funding for hESC research, some states
took the matter of ‘stem cell funding’ into their own
hands. This started with California, where Californians
passed the Proposition 71, i.e., the California
Stem Cell Research and Cures Act in 2004, to establish
the California Institute for Regenerative Medicine
(CIRM) with a $3 billion budget earmarked for
10 years. More recently, in July 2013, the CIRM
governing board has approved a $70-million plan
to establish the Alpha Stem Cell Clinics Network
between academic institutions in the State for conducting
clinical trials of stem cells [29].
After California, other states in the US have
followed suit. These include Maryland with the
passing of the Maryland Stem Cell Research Act
to establish the Maryland Stem Cell Research Fund
(MSCRF) [30]; Texas with the Cancer Prevention
and Research Institute of Texas (CPRIT), Austin,
TX which was earmarked in 2011 with a $3 billion
research fund for 10 years [31]; Kansas with a
new Stem Cell Center at the University of Kansas,
Kansas City, KS starting in July 2013 [32] and New
York with a new Upstate Stem Cell cGMP Facility
Stem Cell Research Center at the University of
Rochester, New York, NY [33].
While new centers are being set up to get into
the ‘stem cell boom’, well-established centers are
expanding at a tremendous rate to lead the ‘stem
cell race.’ In 2011, the Roddenbury Foundation, for
decades the benefactor of the Gladstone Institute in
California, announced the creation of a new Roddenberry
Center for Stem Cell Biology and Medicine
by the UCSF’s Mission Bay campus. Also in
2011, the Sanford Consortium for Regenerative
Medicine was set up in a 132,000 square-foot building
off La Jolla in San Diego, CA, with joint interest
and partnership with five academic institutions
in southern California. Thus, it was no surprise that
San Diego would be hosting the 9th Annual World
Stem Cell Summit in December 2013 [34].
At the same time, other countries around the
world are pushing ahead in the emerging field of
Regenerative Medicine. In Scotland, the $85 million
Scottish Centre for Regenerative Medicine (SCRM)
and the $38 million bio-incubator facility at Edinburgh
(Scotland, UK) were established within the
last 2 years. More recently, in March 2013, Welsh
Economy Minister Edwina Hart announced the endowment
of £100 million in the Life Science Investment
Fund, part of which was to attract bio-medical
companies to relocate to Wales. One of the companies
was the famous Sir Chris Evans’ ReNeuron, involved
in the UK PISCES clinical trial. Sir Chris is Fund and former Chairman of BioMalta in Malta.
Interestingly, because of his various personal
involvements in the stem cell businesses, Sir Chris
is making news lately (albeit not all good). First, a
recent Business Weekly news reported that Sir Chris
was being investigated by the Wales Audit Office for
irregularity of investing public funds [35]. Second,
Sir Chris’ role as special envoy on biotechnology
was terminated by Malta Enterprise, and Sir Chris’
demand for an apology from Malta Prime Minister
Joseph Muscat was flatly denied [36]. Thus, one
needs to do one’s homework when investing in biotechnology
ventures!
Brief Update on Umbilical Cord Blood Stem
Cell Banks. Currently, there are more than 100 public
and 130 private cord blood banks, with a total of
1.5 million units of cord blood stored. It is estimated
that over 30,000 umbilical cord blood transplantations
(UCBT) have been carried out since the first
UCBT performed by Dr. E. Gluckman and Dr. H.E.
Broxmeyer (the pioneers in Umbilical Cord Blood
Transplantation & Banking) 25 years ago in 1988.
On the subject of stem cell transplantation, we owe
everything to the vision of the late Professor Dr. E.
Donnall Thomas, who carried out the first bone marrow
stem cell transplant in 1957 and received the
Nobel Prize in 1990. It was in December 2012 last
year that the 1 millionth blood stem cell transplant
was carried out, marking a major medical milestone
in the history of modern medicine.
Stem Cell Donor Registry, Adult Peripheral
Blood Stem Cell Banking and Adult Induced Stem
Cell Banking. Nowadays, there are worldwide stem
cell registries, viz. Anthony Nolan Registry (Scotland),
National Marrow Donor Program (USA), Be
The Match Registry (USA), OneMatch Stem Cell &
Marrow Network (Canada), China Marrow Donor
Program (China), South Africa Bone Marrow Registry
(South Africa) and others. Their coordinating
efforts have resulted in many successful stem cell
donations. For example, a 24-year-old Navy Seabee
donated his peripheral blood stem cells (PBSC) to
save the life of someone with a fatal blood disease
[37]. Another success story concerns Robin Roberts,
the popular co-anchor of the US television program
“Good Morning America,” who was diagnosed to
have myelodysplastic syndrome. Six months after
a bone marrow stem cell transplant from her older
sister Sally-Ann, Robin returned in February 2013 to
host the #1-rated US morning show [38].
Regarding PBSC banking, I support the Letter
published in Lancet [39] that five Japanese medical
scientists proposed to the Japanese Government
(after the March 11 2011 earthquake and tsunami)
to harvest and cryo-preserve autologous PBSC
from workers at the damaged Fukushima Daiichi
nuclear power plant as soon as possible. I am not
sure what has been done after the above April 30
2011 ‘PBSC-Proposal’. I just hope that Tepco (the
Operator of the Fukushima nuclear plant), with the
recent (September 2013) allocation of almost half a
billion dollars from the Japanese Government, will
take prompt actions to contain the leakages at the
Fukushima plant and to safeguard the well-being of
the workers.
In the mean time, besides Umbilical Cord
Blood Banking and PSBC Banking (which are indeed
worthwhile insurance for one’s future good
health), there is a ‘new kid on-the-block’. Recently,
Cellectis, a French genome technology company,
has launched an ‘Adult iPSC Banking’ service,
which (for now) is meant only for the rich-n-famous.
For US$60,000 (around £40,000), Cellectis
will reprogram the client’s adult skin cells to iPSCs
via Yama-naka’s Nobel-Prize-winning recipe, and
will cryo-preserve the iPSCs at –180 °C in the Cellectis’
laboratories located in the UK, Switzerland,
Singapore, USA and Dubai [40].
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