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additional excerpts - Rudolf Jaenisch

Additional excerpts from our interview with Dr. Jaenisch

 

Stem Cells Portal (SCP):

Work in the field of hESCs involves the use of surplus and donated human embryos.  This has always been a somewhat controversial issue in the public realm, and thus this research has always had to undergo evaluation, regulation, and even approval by people who are not scientists.  How has this affected your work?

Rudolf Jaenisch (RJ):

Well the work with mESCs has of course been untouched by this controversy.  For hESCs, it has affected me because work with non-presidential human ES cells is cumbersome in this country.  If you want to work on your own non-presidential hESC lines, you have to go through the hassles of separating your laboratory and this work from all of the other federally funded research in this area in your lab and your institute.  And it is difficult to raise money or to write a grant for this work, so these are all hurdles, which I think are substantial.

SCP:
As somebody who stands on the frontier of hESC research today, how do you think this will affect the future of hESC research?

RJ:
I think it will be less and less.  The policy in this country (USA) has been so extreme that it only can become better with whoever forms the next administration here.  There are certainly other countries, like Germany, that are extreme, and they are facing even worse problems than we in the US.

SCP:
There are many confusing data that Oct4 has been detected in adult stem cells and tissues. In your opinion, how important is Oct 4 for somatic cell self renewal?

RJ:
I think it was very attractive to think that Oct4, being the key gene that is important for self renewal of ESCs, might also have a role in adult stem cells.  Indeed, there were hundreds of papers that said they found Oct4 expression in adult stem cells, in the gut, blood, skin, etc., but not in the progenitor cells, which are not immortal.  The evidence was either staining for protein, or PCR.  When I looked at most of those data I was really worried, because the controls were not good and the PCR seems to have been really stretched to its limit, and was unconvincing.  So we looked at this very carefully in mice.  We took a mouse and deleted the Oct4 gene in the adult tissues, and asked if it made any difference to the tissue homeostasis in various tissues.  And there was absolutely no difference – we found that the tissue didn’t need Oct4 in the adults.  And then we stressed these mice.  For instance, we irradiated them, to slough off the intestinal epithelium and found that the mice without Oct4 could regenerate their intestinal epithelium as well as the controls. The same results with the blood and the skin – there was no difference in regeneration even when you stressed the system – the Oct4 deficient stem cells renewed the tissues.  Then we asked the question, could we see Oct4 expression in these cells.  By staining we couldn’t see it.  But by PCR, we detected a low signal (10,000 times less than ESC cells).  However, the signal was there regardless of whether or not the gene was there!  We saw the same signal in mice in which we had deleted the gene as in mice which had the gene.  So obviously this was at the limit of PCR detection and the signal was an artifact.  So basically from our studies, and I stress they were in mice, there is no functional role of Oct4.  Hopefully this will put to rest some of this controversy. 

There is also another interesting argument for this.  We also know that Oct4 is a powerful oncogene. If you express Oct4 ectopically in the mouse, they immediately develop tumors. It’s as powerful an oncogene as c-myc.  So if Oct4 was expressed normally as part of the normal adult stem cell renewal, it should show up as an oncogene all over the place, in many tumors, but it never does.  What that says to me is that this gene is so well silenced that it doesn’t get activated, and has no role in adult development.  Putting this together makes me very much doubt the evidence from people who claim it has some role in normal adult stem cells.  This does not mean that in tissue culture cells, under certain circumstances, this gene could not get reactivated.

SCP:
We know many things about the epigenetic background and profile of animal embryos, but not human embryos. There are some studies which claim that intracytoplasmic sperm injection (ICSI) and assisted reproduction can result in humans in Beckwith-Wiedemann (B-W) syndrome. Do you believe it is assisted reproduction itself, or some specific part of these medical treatments, for instance, suboptimal in vitro culture conditions, that is causing this condition?

RJ:
There are several studies indicating that the incidence of B-W does go up several fold, but the number of patients with B-W is still very low.  I think it is a very interesting finding and a concern.  We know from mouse that when you culture embryos in the petri dish, that you do lose imprints of some of the very sensitive genes, and one of the genes is IGF2, which is actually involved in B-W.  It depends on the media composition.  In the mouse, it’s the NaCl concentration that’s important.  And they even see imprinting defects after implantation.  So it is concerning that you might find this in humans.  The issue is that when the embryo is out of the mother and in culture for a couple days under certain medium conditions, you have to worry that you may lose some imprinting on very sensitive genes.  We would like to understand how to avoid this, but you can’t experiment with human embryos. Any study to do this would be very difficult and challenging.  But the incidence of this disease is very low.  You can look at the problem in mice but the results do not necessarily translate to humans.

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.  Are there ways in which you feel we should be educating and including the public in this important work? 

RJ:
This discussion is very important , as there is so much misconception in the public.  I think good science writers have an enormously important role here.  And not just with the public but also with legislators.  It’s amazing how much misinformation there is even among the  legislators. I’ve seen how these issues are discussed and misunderstood.  It’s a very important task for scientists working in this field to be available to inform the public and the legislature about the science and the facts.  And to get the facts out independently of ideology and other considerations.  
We have to take this obligation very seriously.

SCP:
How detrimental, in your opinion, is the fact that the policies on stem cell research are different in so many countries?    

RJ:
I think it very much depends on the country.  In Germany it’s a very contentious issue, and due to their history they have made strict embryo protection laws, which I think are very bad.  In the US there is no law at all.  But there is a ban on federal funding for this research.  I think this has shaped the public opinion.  But there are also some interesting cases with some very conservative senators who are anti-abortionists, but are also staunch supporters of embryonic stem cell research and therapeutic cloning.  I think it is because they see in their families or their friends the potential of this type of research for medicine.  And it immediately changes how they look at this.  So the opinion people have is very personally colored.

SCP:
What do you feel is one of the most important experiences or defining moments in your education, career, or life that has contributed to your success as a researcher?

RJ:
I think when I was a visiting fellow in Beatrice Mintz’s lab that was a most decisive experience for me. I was a postoc in Arnold Levine’s laboratory at the time and he was a very generous advisor.  He taught me how to work with SV-40 and taught me molecular biology, and when I went to Mintz’s lab for 9 months, I learned to think the way she was thinking about development and embryos, and began to combine it with the molecular biology I had learned in Arnold Levine’s lab.   This likely was the most important experience for my subsequent career.  When we injected the DNA into the embryos and made the first transgenic mice, and then when I saw the first mice being born I was blown away.  And they were all normal and we didn’t know what to do with them.  We couldn’t believe it that they might carry the injected DNA.  Importantly I had to figure out how to find the DNA if it was present. Southern blotting or PCR had not been invented yet, so I had to learn techniques such as Nick translation and cot curves to detect DNA sequences, and it took a long time to actually prove that these animals were indeed transgenic.

additional excerpts - Alan Trounson

 

Additional Excerpts from our Interview with Dr. Alan Trounson

Stem Cells Portal (SCP):
Work in the field of human embryonic stem cells involves the use of surplus and donated human embryos.  This has always been a somewhat controversial issue in the public realm, and thus this research has always had to undergo evaluation, regulation, and even approval by people who are not scientists.  How has this affected your work?


Alan Trounson (AT):
I had been subject to a lot of public interest and publicity with the development of IVF in Australia in the late 1970s and 1980s, and there were several issues that we had to deal with in a very public way, such as presenting the arguments in favour of having IVF available to couples, then moving on to genetic diagnosis, and so on.  There were some strong conservative views against these developments, so I have actually been through the publicity associated with this type of research before, and in many ways the arguments for stem cells are very much the same, such as the issue of embryos being discarded or used for research.  I don’t particularly like this process with all the publicity, but scientists have to contribute.  In the case of stem cells, patient advocates also have a very important role, but scientists also play a crucial role in educating the community. 

Because we were very successful in the early days of IVF, we also inherited some very draconian laws with respect to human embryo research, which impeded a lot of our research capacity in the 1980s and early 1990s.  The laws in Victoria, Australia, were intended to prevent the ‘slippery slope” to unethical procedures from happening; they were the first laws anywhere in the world and were very difficult to operate within.  Much of our work them was done in collaboration with people overseas or interstate, by necessity, because it wasn’t possible to do some of the experimental work in Victoria. hESCs are not attracting the same degree of critique, although nuclear transfer (SCNT) has been impeded in some instances.  Whether that has adversely affected outcomes I’m not sure, because SCNT still hasn’t been successful in humans.  Without these problems, would the work have been easier, had a bigger impact, taken the field further forward?  I’m not sure.  The impact of the American President coming out against new hESC derivation certainly impeded the work in the US, until the California (CIRM) and other initiatives got going.  There were some hold ups in research because there was the feeling from some members of the scientific community that this was an area that they shouldn’t work in because career opportunities might be very limited.  Adverse regulations may have kept some of the best scientists from becoming involved hESCs. The advent of programs like the one in California (CIRM) has really changed all that.

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.

AT:
I think it is very much the role of scientists to be involved in education.  I think the public wants to be educated and to have an opinion based on fact.  The internet is a very effective way of providing information, but public presentations and debates are also all part of what science is nowadays, no matter what field you’re in, whether its genetic engineering, new energy sources, etc.  The public wants to know what the thrust of the research is and what the outcomes are likely to be.  And the only people that can really address that in any serious way are the scientists.  It’s a very important role that we have.  We also have to be able to talk in a way that is understood by the public, comprehensible and useful, it’s a language which has to be modified form our own internal scientific language, and teaching people to do that has always been an important role of senior researchers.   

CIRM has many different activities to reach out to the public, such as spotlights on various diseases or conditions, and where we stand today in term of regenerative medicine.  These are generally held at the same time as our board meetings, which are public.  We also work hard on our websites to get information to the public; we have our scientists go out to give talks and we encourage all of the scientists that we fund to talk to the community about what they are doing and why.  It’s very common now to see young people at forums, rotary clubs, interest groups, and so on, talking to other young people about these issues.  At CIRM we have a very comprehensive education program, which we work very hard on, but this is also happening, in many other countries such as Australia, UK, and Sweden.

SCP:
What are some of the biggest challenges you faced as a student and new investigator, and what strategies did you use to meet these challenges?

AT:
The most challenging thing was learning new techniques, such as micromanipulation, molecular biology, etc. The way that I dealt with it was to collaborate with others who had those skills and I could learn from them.  I am also much more the type of scientist who is interested in practical outcomes, so I focused on this.

SCP:
What advice would you give to young scientists in the field today who are trying to balance the demands of work and family/personal life in this increasingly demanding and competitive field?

AT:
My advice would be to reach for the stars!  Try to see something that hasn’t been considered before, take an observation and question why that happened in that case, is this really possible.  Reach out and go beyond the edge and do that work.  It’s exciting and very fulfilling.  It does take a lot of time in the lab, and we are not normally employed to reach out into these areas by the public or private institutions that provide you with the money.  In Australia, we call it skunk time – the time which is not in your normal working hours, when you do some of the really odd experiments that you are interested in yourself – this time can lead to some of the most creative thoughts and exciting observations.  These were unconventional, innovative and creative explorations.  This was one of the most exiting and invigorating times in the lab for me, and very rewarding.

additional excerpts - Christine Mummery

Additional Questions from our Interview with Dr. Christine Mummery

Stem Cells Portal (SCP):
Please describe what fascinates you about hESCs.

Christine Mummery (CM):
I guess maybe the idea that you can control what they do if only you can find the right cues. Our developmental biology research has fed into this extremely well and has provided many of the clues on how to make hESC form cardiomyocytes even better. Also sharing the challenges they have presented (just keeping them undifferentiated and able to form cardiomyocytes in the early years) with like minded colleagues.

SCP:
Please comment about your feelings as to the importance of public discussions and lectures regarding ESC research.

CM:
These are very important, particularly to patient groups to ensure expectations and hope are not turned into hype and clinical trials are not initiated through pressure from the  desperate. The ISSCR is developing guidelines on this. Public lectures are really important in forming the political climate for science and I think as many people as possible should be aware of developments rather than fear of abstract and incorrect ideas of what scientists do with stem cells. I give quite a lot –science cafes, opening of debates, feminist issues on embryo donation, schools.

SCP:
Are there other ways in which you feel we should be educating and including the public in this important work?

CM:
Going into schools is certainly a way of reaching the public young, not only to educate about stem cells but about science in general. Two colleagues and I actually wrote a popular book in Dutch on stem cells which sold extraordinarily well for such a specialist subject. We find it in libraries and schools and many medics in training seem to find it a quick way to get at the basics. In the Netherlands, public debates are often part of developing new laws and these were also a prelude to the Embryo Law here.

SCP:
Do you believe iPS cells will ultimately be most useful as a model to study human disease, or are they likely to provide patient-specific cell therapies?

CM:
I think for studying human disease they could be great but we still need to see phenotypes. I think that is what people are rushing to do right now to be able to answer that question. Patient specific therapies would seem to me to be likely too expensive. Banking of specific HLA types however, may be easier than with hESC. The viral transfer of pluripotency genes still has to be solved of course but I guess that will not take too long.

SCP:
Do you know if some pharmaceutical companies are already using cardiac-differentiated hESCs to test new drugs?

CM:
Interest has grown now that many societies have moved a little on ethical objections and questions of standardization of culture and differentiation are moving along.  GSK has invested heavily in this type of research in the Harvard Stem Cell Institute recently so may be more will follow. Stem Cell for Safer Medicine (SC4SM) in the UK has likewise set up a programme to develop hESC for liver and cardiac drug screening in which Pharma is involved or at least consulted so I think that before long a great deal will be happening. Off target testing is of particular interest as high throughput as well as replacement of animals.

additional excerpts - Ariff Bongso

Additional excerpts from our interview with Dr. Bongso

 

Stem Cells Portal (SCP):

Please explain how you first became interested in hESCs. 

Ariff Bongso (AB):

My training was in Mammalian Reproductive Biology from the Ontario Veterinary College of the University of Guelph, Canada. More specifically, I acquired a wide spectrum of knowledge and skills in the area of ‘Embryo transfer’ and ‘In Vitro Fertilization’ in domestic animals and later went on to apply this to the human in the field of clinical embryology. Although I was trained as a veterinarian with a PhD in ‘comparative reproduction’ I was very keen to apply my skills and knowledge to the human and came to Singapore to take up a faculty position and be attached to  Singapore’s first IVF program in the Department of Obstetrics and Gynaecology of the National University of Singapore in 1987.

SCP:

Work in the field of hESCs involves the use of surplus and donated human embryos.  This has always been a somewhat controversial issue in the public realm, and thus this research has always had to undergo evaluation, regulation, and even approval by people who are not scientists.  How has this affected your work? 

AB:
Thanks to the Singapore government the controversies surrounding hESC research have not been a problem because the regulatory framework was very elegantly developed. The government through the Bioethical Advisory Committee (BAC) comprising of individuals of all walks of life deliberated with the public for over one year to get their feedback on hESC research. Several awareness meetings, discussions and talks were given to the public through various forms of media by stem cell scientists and embryologists about the actual details of the science of stem cell biology. Religious and inter-faith organizations were also involved. The concept and definition of the ‘beginning of life’ was discussed at length between scientists and religious groups and scholars in Singapore and the views presented in the press and other media. Singapore is a multi racial, multi-religious society and it would be difficult to accommodate the views of all groups and so the government through the BAC made their recommendations based on consensus. The larger majority of the public supported hESC research with the only major concern towards reproductive cloning. The guidelines have been finally formulated for stem cell scientists as to what can and what cannot be done with the right checks, balances and penalties. Thus, my research has not been affected because I know where my boundaries lie.

SCP:
What do you see as the nearest practical application of hESC research?

AB:
To me the biggest challenge facing hESC scientists is the elimination of teratoma formation through hESC-derived tissue therapy. I see little interest in this important area as safety is fundamental to taking this science to the clinic. It has been claimed that even a few rogue undifferentiated hESCs in the hESC-derived tissue population can induce teratomas in immunodeficient mice. This thus is a very worrying problem. Once this issue is resolved I believe that the nearest application of hESC research should be for liver diseases (cirrhosis and liver failure). This is because the liver is the only organ that undergoes spontaneous regeneration and is therefore the ‘Holy Grail’ for regenerative medicine. It has its own stem cells, is not a complicated organ like the brain or heart. Injecting just a few hESC-derived hepatocytes may help to trigger of the intrinsic regeneration process in patients with cirrhosis still having a part of intact liver. We can also learn a lot from the regenerative machinery of this organ.

SCP:
Where do you see the potential of hESC and iPS cells to treat human infertility?

AB:
If one is referring to the production of germ cells (male and female gametes) from iPSCs or hESC, I think this is a long shot. Although nice in vitro systems that can help promote differentiation of hESC or iPSCs towards a germ cell lineage have been developed, there would be obstacles at the point of meiosis to produce complete functional gametes for the purpose of human infertility. The molecular mechanisms involved during and after meiosis in vitro, are very complex and would require very complex in vitro environments. In the studies that have  demonstrated ’gamete-like’ structures after hESC differentiation in vitro, I am not sure from a functional point of view whether they can be used for reprogramming or generate embryos with normal embryogenesis.

SCP:
Are there ways in which you feel we should be educating and including the public in this important work? 

AB:
I believe this is very important. I have been personally involved with the Singapore public, giving talks, seminars and discussions using powerpoint slide presentations. These were also delivered to religious organizations. I realized that many religious scholars and members of the public are not familiar with the facts of the science and even presume that hESCs are derived from mature concepti where all organ systems are fully developed. The timing of the beginning of life has also got to be discussed openly from a multi-religious point of view. We did this in a very cordial and harmonious way in Singapore through our inter-faith organization. This helped our national Bioethical Advisory Committee to smoothly make their recommendations and guidelines for hESC research and application through consensus of opinion. The majority of the Singapore public was in favor of hESC research and application. The BAC used the Day-14 rule (beginning of primitive streak formation) where human embryos after Day-14 could not be manipulated and reproductive cloning was disallowed. Given our own experience in Singapore I believe that educating the public on stem cell research is important and extremely useful.

The ways we should be going about this is to make stem cell scientists provide talks together with dialogue sessions on TV and in the Newspapers. A hotline for public feedback is also useful. Involvement of the inter-faith religious organizations is extremely useful as they would be the conduits between stem cell scientists and the public.

SCP:
What are some of the biggest challenges you faced as a student and new investigator, and what strategies did you use to meet these challenges? 

AB:
As a student my biggest barrier was to write a proper scientific article by myself that would be accepted in a journal. I had trouble in writing in scientific English and not knowing where to start and where to end. My initial manuscripts went into pages most of which were redundant. I think the acceptance of my first paper written all by myself made me realize that there were three fundamental questions one had to seek answers to when structuring a manuscript. They are ‘Where are you going’, ‘How are you going’ and ‘Have you got there’. This basically is putting forward a hypothesis and attempting to prove or disprove it. ‘Where are you going’ is clearly seen as the objectives in the ‘Introduction’ section of a manuscript, ‘How are you going’ is the Materials and Methods’ and ‘Have you got there’ is the ‘Results and Discussion’ sections.

Celebrating 10 Years of hESC Cell Lines

Introduction

Ten years ago this November, a paper was published that led to an explosion in the field of stem cell research. In November 1998, Dr. James Thomson’s laboratory reported the first derivation of human embryonic stem cell (hESC) lines from human blastocysts (Science 1998;282:1145–1147).

10 Most Frequently Cited Articles from Stem Cells Journal - Sept 2008

 

The 10 Most-Frequently Cited Articles

in Stem Cells as of October 1, 2008 -- updated monthly

Most-cited rankings are recalculated at the beginning of the month.
Rankings are based on citations to articles on this journal site from articles in
HighWire-hosted journals.

 

1.  Bo-Ra Son, Leah A. Marquez-Curtis, Magda Kucia, Marcin Wysoczynski, A. Robert Turner, Janina Ratajczak, Mariusz Z. Ratajczak, Anna Janowska-Wieczorek

Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases

Stem Cells May 01, 2006; 24: 1254-1264.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (859K)

(Cited 26 times)

 

2.  Susanne Kern, Hermann Eichler, Johannes Stoeve, Harald Klüter, Karen Bieback

Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue

Stem Cells May 01, 2006; 24: 1294-1301.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (505K)

(Cited 23 times)

 

3.  Mauro Krampera, Lorenzo Cosmi, Roberta Angeli, Annalisa Pasini, Francesco Liotta, Angelo Andreini, Veronica Santarlasci, Benedetta Mazzinghi, Giovanni Pizzolo, Fabrizio Vinante, Paola Romagnani, Enrico Maggi, Sergio Romagnani, Francesco Annunziato

Role for Interferon- in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells

Stem Cells Feb 01, 2006; 24: 386-398.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (803K)

(Cited 21 times)

 

4.  Pär Thored, Andreas Arvidsson, Emanuele Cacci, Henrik Ahlenius, Therése Kallur, Vladimer Darsalia, Christine T. Ekdahl, Zaal Kokaia, Olle Lindvall

Persistent Production of Neurons from Adult Brain Stem Cells During Recovery after Stroke

Stem Cells Mar 01, 2006; 24: 739-747.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1080K)

(Cited 19 times)

 

5.  Masako Miura, Yasuo Miura, Hesed M. Padilla-Nash, Alfredo A. Molinolo, Baojin Fu, Vyomesh Patel, Byoung-Moo Seo, Wataru Sonoyama, Jenny J. Zheng, Carl C. Baker, Wanjun Chen, Thomas Ried, Songtao Shi

Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation

Stem Cells Apr 01, 2006; 24: 1095-1103.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (976K)

(Cited 18 times)

 

6.  Erica L. Herzog, John Van Arnam, BuQu Hu, Diane S. Krause

Threshold of Lung Injury Required for the Appearance of Marrow-Derived Lung Epithelia

Stem Cells Aug 01, 2006; 24: 1986-1992.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (259K)

(Cited 17 times)

 

7.  Naotsugu Haraguchi, Tohru Utsunomiya, Hiroshi Inoue, Fumiaki Tanaka, Koshi Mimori, Graham F. Barnard, Masaki Mori

Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

Stem Cells Mar 01, 2006; 24: 506-513.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (487K)

(Cited 17 times)

 

8.  Marek Honczarenko, Yi Le, Marcin Swierkowski, Ionita Ghiran, Aleksandra M. Glodek, Leslie E. Silberstein

Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Stem Cells Apr 01, 2006; 24: 1030-1041.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1934K)

(Cited 16 times)

 

9.  Eva Rohde, Christina Malischnik, Daniela Thaler, Theresa Maierhofer, Werner Linkesch, Gerhard Lanzer, Christian Guelly, Dirk Strunk

Blood Monocytes Mimic Endothelial Progenitor Cells

Stem Cells Feb 01, 2006; 24: 357-367.
(In "TISSUE-SPECIFIC STEM CELLS")    AbstractReferences |  Full Text: HTML, PDF (1248K)

(Cited 16 times)

 

10.  Jakub Tolar, Alma J. Nauta, Mark J. Osborn, Angela Panoskaltsis Mortari, Ron T. McElmurry, Scott Bell, Lily Xia, Ning Zhou, Megan Riddle, Tania M. Schroeder, Jennifer J. Westendorf, R. Scott McIvor, Pancras C.W. Hogendoorn, Karoly Szuhai, LeAnn Oseth, Betsy Hirsch, Stephen R. Yant, Mark A. Kay, Alexandra Peister, Darwin J. Prockop, Willem E. Fibbe, Bruce R. Blazar

Sarcoma Derived from Cultured Mesenchymal Stem Cells

Stem Cells Feb 01, 2007; 25: 371-379.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (861K)

(Cited 15 times)

10 Most Frequently Cited Articles from Stem Cells Journal - Nov 2008

 

The 10 Most-Frequently Cited Articles

in Stem Cells as of December 1, 2008 -- updated monthly

Most-cited rankings are recalculated at the beginning of the month.
Rankings are based on citations to articles on this journal site from articles in
HighWire-hosted journals.

 

1.   Bo-Ra Son, Leah A. Marquez-Curtis, Magda Kucia, Marcin Wysoczynski, A. Robert Turner, Janina Ratajczak, Mariusz Z. Ratajczak, Anna Janowska-Wieczorek

Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases

Stem Cells May 01, 2006; 24: 1254-1264.
(In "TISSUE-SPECIFIC STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (859K)

(Cited 27 times)

 

2.   Susanne Kern, Hermann Eichler, Johannes Stoeve, Harald Klüter, Karen Bieback

Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue

Stem Cells May 01, 2006; 24: 1294-1301.
(In "TISSUE-SPECIFIC STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (505K)

(Cited 23 times)

 

3.   Mauro Krampera, Lorenzo Cosmi, Roberta Angeli, Annalisa Pasini, Francesco Liotta, Angelo Andreini, Veronica Santarlasci, Benedetta Mazzinghi, Giovanni Pizzolo, Fabrizio Vinante, Paola Romagnani, Enrico Maggi, Sergio Romagnani, Francesco Annunziato

Role for Interferon- in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells

Stem Cells Feb 01, 2006; 24: 386-398.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")  
AbstractReferences |  Full Text: HTML, PDF (803K)

(Cited 21 times)

 

4.   Erica L. Herzog, John Van Arnam, BuQu Hu, Diane S. Krause

Threshold of Lung Injury Required for the Appearance of Marrow-Derived Lung Epithelia

Stem Cells Aug 01, 2006; 24: 1986-1992.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")  
AbstractReferences |  Full Text: HTML, PDF (259K)

(Cited 18 times)

 

5.   Marek Honczarenko, Yi Le, Marcin Swierkowski, Ionita Ghiran, Aleksandra M. Glodek, Leslie E. Silberstein

Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Stem Cells Apr 01, 2006; 24: 1030-1041.
(In "TISSUE-SPECIFIC STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (1934K)

(Cited 19 times)

 

6.  Pär Thored, Andreas Arvidsson, Emanuele Cacci, Henrik Ahlenius, Therése Kallur, Vladimer Darsalia, Christine T. Ekdahl, Zaal Kokaia, Olle Lindvall

Persistent Production of Neurons from Adult Brain Stem Cells During Recovery after Stroke

Stem Cells Mar 01, 2006; 24: 739-747.
(In "TISSUE-SPECIFIC STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (1080K)

(Cited 19 times)

 

7.  Masako Miura, Yasuo Miura, Hesed M. Padilla-Nash, Alfredo A. Molinolo, Baojin Fu, Vyomesh Patel, Byoung-Moo Seo, Wataru Sonoyama, Jenny J. Zheng, Carl C. Baker, Wanjun Chen, Thomas Ried, Songtao Shi

Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation

Stem Cells Apr 01, 2006; 24: 1095-1103.
(In "TISSUE-SPECIFIC STEM CELLS") 
[Abstract]
[Full Text] [PDF]

(Cited 18 times)

 

8.  Naotsugu Haraguchi, Tohru Utsunomiya, Hiroshi Inoue, Fumiaki Tanaka, Koshi Mimori, Graham F. Barnard, Masaki Mori

Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

Stem Cells Mar 01, 2006; 24: 506-513.
(In "CANCER STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (976K)

(Cited 18 times)

 

9.  Eva Rohde, Christina Malischnik, Daniela Thaler, Theresa Maierhofer, Werner Linkesch, Gerhard Lanzer, Christian Guelly, Dirk Strunk

Blood Monocytes Mimic Endothelial Progenitor Cells

Stem Cells Feb 01, 2006; 24: 357-367.
(In "TISSUE-SPECIFIC STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (1248K)

(Cited 16 times)

 

10.   Jakub Tolar, Alma J. Nauta, Mark J. Osborn, Angela Panoskaltsis Mortari, Ron T. McElmurry, Scott Bell, Lily Xia, Ning Zhou, Megan Riddle, Tania M. Schroeder, Jennifer J. Westendorf, R. Scott McIvor, Pancras C.W. Hogendoorn, Karoly Szuhai, LeAnn Oseth, Betsy Hirsch, Stephen R. Yant, Mark A. Kay, Alexandra Peister, Darwin J. Prockop, Willem E. Fibbe, Bruce R. Blazar

Sarcoma Derived from Cultured Mesenchymal Stem Cells

Stem Cells Feb 01, 2007; 25: 371-379.
(In "CANCER STEM CELLS")  
AbstractReferences |  Full Text: HTML, PDF (861K)

(Cited 15 times)

 

10 Most Frequently Cited Articles from Stem Cells Journal - Dec 2008

 

The 10 Most-Frequently Cited Articles

in Stem Cells as of January 1, 2009 -- updated monthly

Most-cited rankings are recalculated at the beginning of the month.
Rankings are based on citations to articles on this journal site from articles in HighWire-hosted journals.

 

1.    Bo-Ra Son, Leah A. Marquez-Curtis, Magda Kucia, Marcin Wysoczynski, A. Robert Turner, Janina Ratajczak, Mariusz Z. Ratajczak, Anna Janowska-Wieczorek

Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases

Stem Cells May 01, 2006; 24: 1254-1264.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (859K)

(Cited 27 times)

 

2.    Susanne Kern, Hermann Eichler, Johannes Stoeve, Harald Klüter, Karen Bieback

Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue

Stem Cells May 01, 2006; 24: 1294-1301.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (505K)

(Cited 23 times)

 

3.    Mauro Krampera, Lorenzo Cosmi, Roberta Angeli, Annalisa Pasini, Francesco Liotta, Angelo Andreini, Veronica Santarlasci, Benedetta Mazzinghi, Giovanni Pizzolo, Fabrizio Vinante, Paola Romagnani, Enrico Maggi, Sergio Romagnani, Francesco Annunziato

Role for Interferon- in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells

Stem Cells Feb 01, 2006; 24: 386-398.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (803K)

(Cited 21 times)

 

4.    Pär Thored, Andreas Arvidsson, Emanuele Cacci, Henrik Ahlenius, Therése Kallur, Vladimer Darsalia, Christine T. Ekdahl, Zaal Kokaia, Olle Lindvall

Persistent Production of Neurons from Adult Brain Stem Cells During Recovery after Stroke

Stem Cells Mar 01, 2006; 24: 739-747.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1080K)

(Cited 20 times)

 

5.    Erica L. Herzog, John Van Arnam, BuQu Hu, Diane S. Krause

Threshold of Lung Injury Required for the Appearance of Marrow-Derived Lung Epithelia

Stem Cells Aug 01, 2006; 24: 1986-1992.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (259K)

(Cited 19 times)

 

6.    Masako Miura, Yasuo Miura, Hesed M. Padilla-Nash, Alfredo A. Molinolo, Baojin Fu, Vyomesh Patel, Byoung-Moo Seo, Wataru Sonoyama, Jenny J. Zheng, Carl C. Baker, Wanjun Chen, Thomas Ried, Songtao Shi

Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation

Stem Cells Apr 01, 2006; 24: 1095-1103.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (976K)

(Cited 19 times)

 

7.    Marek Honczarenko, Yi Le, Marcin Swierkowski, Ionita Ghiran, Aleksandra M. Glodek, Leslie E. Silberstein

Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Stem Cells Apr 01, 2006; 24: 1030-1041.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1934K)

(Cited 19 times)

 

8.    Eva Rohde, Christina Malischnik, Daniela Thaler, Theresa Maierhofer, Werner Linkesch, Gerhard Lanzer, Christian Guelly, Dirk Strunk

Blood Monocytes Mimic Endothelial Progenitor Cells

Stem Cells Feb 01, 2006; 24: 357-367.
(In "TISSUE-SPECIFIC STEM CELLS")    AbstractReferences |  Full Text: HTML, PDF (1248K)

(Cited 19 times)

 

9.    Naotsugu Haraguchi, Tohru Utsunomiya, Hiroshi Inoue, Fumiaki Tanaka, Koshi Mimori, Graham F. Barnard, Masaki Mori

Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

Stem Cells Mar 01, 2006; 24: 506-513.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (487K)

(Cited 18 times)

 

10.  Jakub Tolar, Alma J. Nauta, Mark J. Osborn, Angela Panoskaltsis Mortari, Ron T. McElmurry, Scott Bell, Lily Xia, Ning Zhou, Megan Riddle, Tania M. Schroeder, Jennifer J. Westendorf, R. Scott McIvor, Pancras C.W. Hogendoorn, Karoly Szuhai, LeAnn Oseth, Betsy Hirsch, Stephen R. Yant, Mark A. Kay, Alexandra Peister, Darwin J. Prockop, Willem E. Fibbe, Bruce R. Blazar

Sarcoma Derived from Cultured Mesenchymal Stem Cells

Stem Cells Feb 01, 2007; 25: 371-379.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (861K)

(Cited 16 times)

 

 

10 Most Frequently Cited Articles from Stem Cells Journal - Jan 2009

 

The 10 Most-Frequently Cited Articles

in Stem Cells as of February 1, 2009 -- updated monthly

Most-cited rankings are recalculated at the beginning of the month.
Rankings are based on citations to articles on this journal site from articles in HighWire-hosted journals.

 

1.    Bo-Ra Son, Leah A. Marquez-Curtis, Magda Kucia, Marcin Wysoczynski, A. Robert Turner, Janina Ratajczak, Mariusz Z. Ratajczak, Anna Janowska-Wieczorek

Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases

Stem Cells May 01, 2006; 24: 1254-1264.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (859K)

(Cited 28 times)

 

2.    Susanne Kern, Hermann Eichler, Johannes Stoeve, Harald Klüter, Karen Bieback

Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue

Stem Cells May 01, 2006; 24: 1294-1301.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (505K)

(Cited 24 times)

 

3.    Mauro Krampera, Lorenzo Cosmi, Roberta Angeli, Annalisa Pasini, Francesco Liotta, Angelo Andreini, Veronica Santarlasci, Benedetta Mazzinghi, Giovanni Pizzolo, Fabrizio Vinante, Paola Romagnani, Enrico Maggi, Sergio Romagnani, Francesco Annunziato

Role for Interferon- in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells

Stem Cells Feb 01, 2006; 24: 386-398.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (803K)

(Cited 22 times)

 

4.    Pär Thored, Andreas Arvidsson, Emanuele Cacci, Henrik Ahlenius, Therése Kallur, Vladimer Darsalia, Christine T. Ekdahl, Zaal Kokaia, Olle Lindvall

Persistent Production of Neurons from Adult Brain Stem Cells During Recovery after Stroke

Stem Cells Mar 01, 2006; 24: 739-747.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1080K)

(Cited 21 times)

 

5.    Masako Miura, Yasuo Miura, Hesed M. Padilla-Nash, Alfredo A. Molinolo, Baojin Fu, Vyomesh Patel, Byoung-Moo Seo, Wataru Sonoyama, Jenny J. Zheng, Carl C. Baker, Wanjun Chen, Thomas Ried, Songtao Shi

Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation

Stem Cells Apr 01, 2006; 24: 1095-1103.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (976K)

(Cited 20 times

 

6.    Jakub Tolar, Alma J. Nauta, Mark J. Osborn, Angela Panoskaltsis Mortari, Ron T. McElmurry, Scott Bell, Lily Xia, Ning Zhou, Megan Riddle, Tania M. Schroeder, Jennifer J. Westendorf, R. Scott McIvor, Pancras C.W. Hogendoorn, Karoly Szuhai, LeAnn Oseth, Betsy Hirsch, Stephen R. Yant, Mark A. Kay, Alexandra Peister, Darwin J. Prockop, Willem E. Fibbe, Bruce R. Blazar

Sarcoma Derived from Cultured Mesenchymal Stem Cells

Stem Cells Feb 01, 2007; 25: 371-379.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (861K)

(Cited 19 times)

 

7.    Erica L. Herzog, John Van Arnam, BuQu Hu, Diane S. Krause

Threshold of Lung Injury Required for the Appearance of Marrow-Derived Lung Epithelia

Stem Cells Aug 01, 2006; 24: 1986-1992.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (259K)

(Cited 19 times)

 

8.    Marek Honczarenko, Yi Le, Marcin Swierkowski, Ionita Ghiran, Aleksandra M. Glodek, Leslie E. Silberstein

Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Stem Cells Apr 01, 2006; 24: 1030-1041.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1934K)

(Cited 19 times)

 

9.    Eva Rohde, Christina Malischnik, Daniela Thaler, Theresa Maierhofer, Werner Linkesch, Gerhard Lanzer, Christian Guelly, Dirk Strunk

Blood Monocytes Mimic Endothelial Progenitor Cells

Stem Cells Feb 01, 2006; 24: 357-367.
(In "TISSUE-SPECIFIC STEM CELLS")    AbstractReferences |  Full Text: HTML, PDF (1248K)

(Cited 19 times)

 

10.  Naotsugu Haraguchi, Tohru Utsunomiya, Hiroshi Inoue, Fumiaki Tanaka, Koshi Mimori, Graham F. Barnard, Masaki Mori

Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

Stem Cells Mar 01, 2006; 24: 506-513.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (487K)

(Cited 18 times)

 

 

10 Most Frequently Cited Articles from Stem Cells Journal - Feb 2009

The 10 Most-Frequently Cited Articles

in Stem Cells as of March 1, 2009 -- updated monthly

Most-cited rankings are recalculated at the beginning of the month.
Rankings are based on citations to articles on this journal site from articles in HighWire-hosted journals.

 

1.    Bo-Ra Son, Leah A. Marquez-Curtis, Magda Kucia, Marcin Wysoczynski, A. Robert Turner, Janina Ratajczak, Mariusz Z. Ratajczak, Anna Janowska-Wieczorek

Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases

Stem Cells May 01, 2006; 24: 1254-1264.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (859K)

(Cited 28 times)

 

2.    Susanne Kern, Hermann Eichler, Johannes Stoeve, Harald Klüter, Karen Bieback

Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue

Stem Cells May 01, 2006; 24: 1294-1301.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (505K)

(Cited 24 times)

 

3.    Mauro Krampera, Lorenzo Cosmi, Roberta Angeli, Annalisa Pasini, Francesco Liotta, Angelo Andreini, Veronica Santarlasci, Benedetta Mazzinghi, Giovanni Pizzolo, Fabrizio Vinante, Paola Romagnani, Enrico Maggi, Sergio Romagnani, Francesco Annunziato

Role for Interferon- in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells

Stem Cells Feb 01, 2006; 24: 386-398.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (803K)

(Cited 22 times)

 

4.    Pär Thored, Andreas Arvidsson, Emanuele Cacci, Henrik Ahlenius, Therése Kallur, Vladimer Darsalia, Christine T. Ekdahl, Zaal Kokaia, Olle Lindvall

Persistent Production of Neurons from Adult Brain Stem Cells During Recovery after Stroke

Stem Cells Mar 01, 2006; 24: 739-747.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1080K)

(Cited 21 times)

 

5.    Masako Miura, Yasuo Miura, Hesed M. Padilla-Nash, Alfredo A. Molinolo, Baojin Fu, Vyomesh Patel, Byoung-Moo Seo, Wataru Sonoyama, Jenny J. Zheng, Carl C. Baker, Wanjun Chen, Thomas Ried, Songtao Shi

Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation

Stem Cells Apr 01, 2006; 24: 1095-1103.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (976K)

(Cited 20 times)

 

6.    Marek Honczarenko, Yi Le, Marcin Swierkowski, Ionita Ghiran, Aleksandra M. Glodek, Leslie E. Silberstein

Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Stem Cells Apr 01, 2006; 24: 1030-1041.
(In "TISSUE-SPECIFIC STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (1934K)

(Cited 20 times)

 

7.    Jakub Tolar, Alma J. Nauta, Mark J. Osborn, Angela Panoskaltsis Mortari, Ron T. McElmurry, Scott Bell, Lily Xia, Ning Zhou, Megan Riddle, Tania M. Schroeder, Jennifer J. Westendorf, R. Scott McIvor, Pancras C.W. Hogendoorn, Karoly Szuhai, LeAnn Oseth, Betsy Hirsch, Stephen R. Yant, Mark A. Kay, Alexandra Peister, Darwin J. Prockop, Willem E. Fibbe, Bruce R. Blazar

Sarcoma Derived from Cultured Mesenchymal Stem Cells

Stem Cells Feb 01, 2007; 25: 371-379.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (861K)

(Cited 19 times)

 

8.    Erica L. Herzog, John Van Arnam, BuQu Hu, Diane S. Krause

Threshold of Lung Injury Required for the Appearance of Marrow-Derived Lung Epithelia

Stem Cells Aug 01, 2006; 24: 1986-1992.
(In "TRANSLATIONAL AND CLINICAL RESEARCH")   AbstractReferences |  Full Text: HTML, PDF (259K)

(Cited 19 times)

 

9.    Naotsugu Haraguchi, Tohru Utsunomiya, Hiroshi Inoue, Fumiaki Tanaka, Koshi Mimori, Graham F. Barnard, Masaki Mori

Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

Stem Cells Mar 01, 2006; 24: 506-513.
(In "CANCER STEM CELLS")   AbstractReferences |  Full Text: HTML, PDF (487K)

(Cited 19 times)

 

10.  Eva Rohde, Christina Malischnik, Daniela Thaler, Theresa Maierhofer, Werner Linkesch, Gerhard Lanzer, Christian Guelly, Dirk Strunk

Blood Monocytes Mimic Endothelial Progenitor Cells

Stem Cells Feb 01, 2006; 24: 357-367.
(In "TISSUE-SPECIFIC STEM CELLS")    AbstractReferences |  Full Text: HTML, PDF (1248K)

(Cited 19 times)

 

 

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