Talking Points on iPS Cells
Adult Stem Cells Treat MS and Arthritis in Mice
NEW! Reprogrammed Skin Cells Strut Their Stuff (8Dec07)
Researchers Turn Skin Cells Into Pluripotent Stem Cells (20Nov07)
Scientists Discover How to Isolate Stem Cells in Womb Tissue
Cord Blood Registry Sees Strong Growth in Charitable Banking Program
Menstrual Blood Could Be A Rich Source of Adult Stem Cells (JTM, 07)…
Talking Points on iPS Cells — http://stemcellresearch.org/statement/pptalkingpointsweb.pdf
ADULT STEM CELLS TREAT MS AND ARTHRITIS IN MICE. As we celebrate the creation and potential of induced Pluripotent Stem Cells, adult stem cell research at Stanford University finds that blood stem cells taken from a donor with a healthy immune system effectively treated multiple sclerosis and arthritis in mice.
From the story in the Telegraph:
Thousands of patients with arthritis and multiple sclerosis are given new hope today by scientists who have developed a way to alter the immune system.
Both conditions are caused when the immune system becomes faulty and attacks the body. Scientists have discovered that by injecting stem cells, the body's building blocks, taken from a healthy donor into the patient they can effectively transplant the donor's immune system and cure the condition.
Until now, such a transplant would have been possible only by giving the patient aggressive treatments such as radiotherapy to wipe out the faulty immune system before carrying out a bone marrow transplant to provide new cells. But under the new system patients would be treated with a toxin to clear out the old immune system before being injected with healthy stem cells that would form a new immune system.
The procedure has been performed only on mice but the researchers at Stanford University School of Medicine in California said the "benefits are potentially huge" for humans and could be used to treat MS and rheumatoid arthritis.
The human cloning research advocate Irving Weissman, who is also controversial for wanting to create mice with human brains, is the moving force behind this research. Good on him.
Here's some more from the story:
When the team transplanted new, blood-forming stem cells into the mice, they became attached to the bone marrow and established a new blood and immune system. In this way, stem cells can be taken from a donor and implanted into a person with a good tissue match who has an auto-immune disease, such as multiple sclerosis, so that the new immune system will no longer attack the nerves of the body.
First, the researchers need to do more animal testing and then to develop a way to carry out the same kind of surgical strike on human bloodforming cells.
That last bit is worth noting because it demonstrates, once again, the utter falsity of animal liberationists' ideologically-driven contention that humans receive no benefit from animal research. [Telegraph; 22Nov07, posted by Wesley J. Smith, http://www.wesleyjsmith.com/blog/2007/11/good-news-just-keeps-on-coming-adult.html]
REPROGRAMMED SKIN CELLS STRUT THEIR STUFF. Skin cells reprogrammed to act like embryonic stem cells–a breakthrough first reported in human cells 2 weeks ago–are already showing promise as a therapeutic agent. In 6Dec07 online edition of Science, researchers describe using induced pluripotent stem (iPS) cells to alleviate symptoms of sickle cell anemia in mice. The technique is not yet safe to try in people, but scientists say it is proof of principle that iPS cells could someday treat human disease.
Induced pluripotent stem cells excite scientists because they represent a way to obtain custom-made stem cells without the ethical hurdles of using embryos or oocytes (ScienceNOW, 20 November). Researchers hope that they might be able to use the technique to replace faulty cells in the body with healthy cells containing the patient's own DNA.
Tim Townes of the University of Alabama, Birmingham, and his colleagues wondered whether iPS cells might prove useful in a mouse model of sickle cell anemia. (Blood cells are much easier to replace than are cells that make up tissue.)
In afflicted humans, red blood cells become curved and can't easily flow through blood vessels. The mice show many of the symptoms that human patients do, and so they were an especially good candidate to test iPS cells' abilities, says stem cell researcher Rudolf Jaenisch of the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology, both in Cambridge, who collaborated with Townes on the project.
The first step was creating iPS cells specific to the mice. The researchers took skin cells from the tails of sickle cell mice and inserted copies of four genes that made the cells take on the characteristics of embryonic stem cells. They also added a corrected hemoglobin gene into the cells and coaxed them into becoming blood-producing stem cells. Finally, the researchers injected these partially differentiated cells into sickle cell mice that had been treated with radiation to kill their own blood stem cells. Within a few weeks, the new cells were producing mature blood cells, and the symptoms of sickle cell disease had dramatically improved, the team reports.
Townes says he and Jaenisch initially collaborated on a project that used nuclear transfer to make corrected stem cells, a process called therapeutic cloning. But the experiments failed, he says, because nuclear transfer was too inefficient to produce the needed cells. The iPS cell technique "is amazingly efficient," he says.
The paper is an important step forward, says Jose Cibelli of Michigan State University in East Lansing. The lab results for iPS cells have been impressive so far, he says, "but if they do not have therapeutic value, they will be far from getting to the point of replacing the whole idea of therapeutic cloning."
The important next step for the field, Cibelli says, is to find reliable ways t
o differentiate the cells into a variety of useful cell types and to be sure that no undifferentiated cells remain to cause potential tumors. Other experiments with iPS cells have suggested that they might be prone to causing cancer, but none of the treated mice showed any signs of tumors after 12 weeks. That is a promising sign, Townes says, but much longer studies would be needed before the technique could be considered safe enough to try in humans.
[6Dec07, Gretchen Vogel, ScienceNOW Daily News, http://sciencenow.sciencemag.org/cgi/content/full/2007/1206/2; Family Research Council, 8Dec07]
RESEARCHER TURN SKIN CELLS INTO PLURIPOTENT STEM CELLS. Scientists have managed to reprogram human skin cells directly into cells that look and act like embryonic stem (ES) cells. The technique makes it possible to generate patient-specific stem cells to study or treat disease without using embryos or oocytes–and therefore could bypass the ethical debates that have plagued the field. "This is like an earthquake for both the science and politics of stem cell research," says Jesse Reynolds, policy analyst for the Center for Genetics and Society in Oakland, California.
The work builds on a study published last year by Shinya Yamanaka of Kyoto University in Japan, which showed that mouse tail cells could be transformed into ES-like cells by inserting four genes (ScienceNOW, 3 July 2006). Those genes are normally switched off after embryonic cells differentiate into the various cell types. In June this year, Yamanaka and another group reported that the cells were truly pluripotent, meaning that they had the potential to grow into any tissue in the body (ScienceNOW, 6 June).
Now the race to repeat the feat in human cells has ended in a tie: Two groups report today that they have reprogrammed human skin cells into so-called induced pluripotent cells (iPSs). In a paper published online in Cell, Yamanaka and his colleagues show that their mouse technique works with human cells as well.
And in a paper published online in Science, James Thomson of the University of Wisconsin, Madison, and his colleagues report success in reprogramming human cells, again by inserting just four genes, two of which are different from those Yamanaka uses.
In the new work, Yamanaka and his colleagues used a retrovirus to ferry into adult cells the same four genes they had previously used to reprogram mouse cells: OCT3/4, SOX2, KLF4, and c-MYC.
They reprogrammed cells taken from the facial skin of a 36-year-old woman and from connective tissue from a 69-year-old man. Roughly one iPS cell line was produced for every 5000 cells the researchers treated using the technique, an efficiency that enabled them to produce several cell lines from each experiment.
Thomson's team started from scratch, identifying its own list of 14 candidate reprogramming genes. Like Yamanaka's group, the team used a systematic process of elimination to identify four factors: OCT3 and SOX2, as Yamanaka used, and two different genes, NANOG and LIN28. The group reprogrammed cells from fetal skin and from the foreskin of a newborn boy. The researchers were able to transform about one in 10,000 cells, less than Yamanaka's technique achieved, Thomson says, but still enough to create several cell lines from a single experiment.
Although promising, both techniques share a downside. The retroviruses used to insert the genes could cause tumors in tissues grown from the cells. The crucial next step, everyone agrees, is to find a way to reprogram cells by switching on the genes rather than inserting new copies.
The field is moving quickly toward that goal, says stem cell researcher Douglas Melton of Harvard University. "It is not hard to imagine a time when you could add small molecules that would tickle the same networks as these genes" and produce reprogrammed cells without genetic alterations, he says.
Once the kinks are worked out, "the whole field is going to completely change," says stem cell researcher Jose Cibelli of Michigan State University in East Lansing. "People working on ethics will have to find something new to worry about."
For a more in-depth news story on this topic, see this week's issue of Science, available online 22 November. [20 November 2007, Gretchen Vogel, ScienceNOW Daily News, http://sciencenow.sciencemag.org/cgi/content/full/2007/1120/1]
SCIENTISTS DISCOVER HOW TO ISOLATE STEM CELLS IN WOMB TISSUE. Scientists in Australia have found a way of identifying probable stem cells in the lining of women’s wombs. The finding opens up the possibility of using the stem cells for tissue engineering applications such as building up natural tissue to repair prolapsed pelvic floors. Pelvic floor prolapse is a common condition, affecting over 50% of women after childbirth; around one in ten women have surgery and a third of these women require repeated operations to correct the problem.
In research published online today (Thursday 13 September) in the journal Human Reproduction, Dr Caroline Gargett describes how she and her PhD student, Ms Kjiana Schwab, identified two markers, CD146 and PDGF-Rß, which they were able to use to isolate mesenchymal stem-like cells (MSC) from endometrial tissue using a high speed cell sorting machine (fluorescence activated cell sorting – FACS). Only 1.5% of the endometrial cells sorted in this way expressed both markers and, therefore could be MSC.
They then investigated the properties of the MSC to discover whether they really were stem cells, capable of differentiating into a variety of different cell types. They found the cells were able to produce clones to form colonies of new cells at a rate that was 15 times greater than produced by the other endometrial cells. Furthermore, the MSC were able to differentiate into fat, bone, cartilage and smooth muscle cells in the culture dish. The MSC also appeared to be located around blood vessels in the endometrium (perivascular region).
Dr Gargett, a senior scientist at the Centre for Women’s Health Research, Monash Institute of Medical Research, Monash University, Victoria, Australia, explained: “Colony-forming ability is a property of adult stem cells, as is the ability to differentiate into different cell types. The fact that the cells expressing the two markers were located in the perivascular region strengthens our case that we have isolated mesenchymal stem cells, because mesenchymal stem cells from bone marrow and fat are found around blood vessels too. It also gives us clues as to how they might function in repairing and regenerating new endometrium each month.”
This is the first time that researchers have been able to use markers to isolate MSC from the endometrium and also the first study to show that the properties of these cells mean they are highly likely to be stem cells.
Dr Gargett said: “We had previously detected that MSC were present in the human endometrium but we were unable to isolate the MSC, which was a big drawback in studying their properties. The major finding of this study was the identification of two markers which enabled the prospective isolation of MSC-like cells from human endometrial tissue. This allows us to characterise endometrial MSC so we can understand their molecular and cellular properties better, compare them to MSC
from other sources, such as bone marrow and fat, use them for tissue engineering applications, such as making constructs with biological scaffolds for pelvic floor prolapse surgery, and find where they are located in endometrium (i.e. around blood vessels); this gives us a clue as to how they might function in growing new endometrium each menstrual cycle and how they may have a role in gynaecological diseases such as endometriosis.”
The human endometrium is the only adult tissue that contains a substantial amount of the connective tissue framework (called stroma) that regularly regenerates under normal conditions when a woman menstruates. Because of its regenerative properties, Dr Gargett believed that it might contain MSC that were responsible for the monthly regeneration of the stroma and related blood vessels, and which could be an easily available source of MSC for stem cell therapy. However, until she identified CD146 and PDGF-Rß as MSC markers, there were no known markers and therefore no way of isolating the endometrial MSC.
Her research, using tissue obtained from women aged between 31-49 who were having hysterectomies, indicates that the MSC are probably located mainly in the basalis layer of the endometrium, which is the layer that is not shed during a woman’s period. “We think that is where the MSC should be if they are responsible for producing the functionalis layer, which grows each month,” said Dr Gargett.
This means that, although it might be possible to collect MSC from menstrual blood, the most likely method of collection would be curettage or biopsy. “This would not be any more invasive than collecting MSC from bone marrow or surgical removal (biopsy) of fat tissue,” said Dr Gargett. “MSC could also be collected from postmenopausal women, whose endometrium is very thin. If these women are given oestrogen replacement therapy for a very short time (a week or two) their endometrium will grow to the thickness of a reproductive age woman and the MSC could be collected without harm to the woman.”
Dr Gargett believes that initial applications for endometrial MSC would be to use them on the women that they had been retrieved from (rather than on other people) for gynaecological purposes such as pelvic floor prolapse. “Pelvic floor prolapse is a common problem that significantly impacts the lives of many women and they find it embarrassing to talk about – it is a hidden disorder in need of an innovative therapy,” she explained.
“Clinicians have been using a synthetic mesh as a reinforcement material to try and reduce the high rate of recurrence of this condition. While these meshes are often successful, a significant number of complications arise due to erosion or rejection of the foreign material. Increasingly clinicians have been trying biological scaffold material, but this often fails as it lacks cells and the body breaks it down faster than the body’s cells can infiltrate and strengthen the material. We believe that using a combination of biological scaffold and a woman’s own MSC might provide a solution that would ensure a longer lasting firm natural tissue that would be a superior support for the prolapsed uterus.
“We also believe that the identification of the MSC in human endometrium gives us the opportunity to investigate their possible role in the development and pathogenesis of common gynaecological disorders associated with abnormal endometrial growth, such as endometriosis and adenomyosis.”
However, it will probably be at least ten years before applications from Dr Gargett’s findings will be used in the clinic. The next stages of the research include refining the technique by looking for further markers and possibly a single marker that could do the same job as two, and testing the possible tissue-engineering applications in animal models before they are used in humans.
Source: European Society for Human Reproduction and Embryology, Human Reproduction, 13Nov07; http://www.physorg.com/news108880605.html, 13November2007]
CORD BLOOD REGISTRY SEES STRONG GROWTH IN CHARITABLE BANKING PROGRAM. Cord Blood Registry (CBR), one of the world's largest stem cells banks, announced last week that its no-cost banking service to help families with a critical medical need, has achieved record growth in 2007, enrolling 35 percent more newborns than last year.
Its programs offer expectant parents the opportunity to bank the cord blood of their newborn at no cost when another family member has been diagnosed with a condition that may require a stem cell transplant. Pro-life groups herald the use of such adult stem cells because they offer an ethical alternative to embryonic stem cell research — which still requires the destruction of human life.
CBR's Designated Transplant Program was launched in 1996 and, to date, nearly 2,000 newborns have been enrolled in the program and their cord blood stem cells are ready and immediately available for the designated family member who may need them.
Research has shown that cord blood stem cells match more easily with family members than bone marrow, and genetically-related cord blood stem cells lead to better transplant outcomes, including less transplant-related mortality and a lower incidence of medical complications like rejection.
Tom Moore, chief executive officer of CBR, told LifeNews.com, "As more physicians educate expectant parents about the medical benefits of cord blood stem cells, more lives can be saved." For more information about CBR, visit www.CordBlood.com. [3Dec07, San Bruno, CA LifeNews.com]
MENSTRUAL BLOOD COULD BE A RICH SOURCE OF ADULT STEM CELLS. The "monthly curse" may be anything but: menstrual blood appears to be a rich and easily accessible source of unique adult stem cells termed Endometrial Regenerative Cells (ERC), claim two competing research groups.
Each month, after a woman’s uterine lining is shed, it has to be rebuilt in preparation for a fertilized egg. This feat involves growing the billions of cells making up the 5 millimetre-thick lining in just seven days.
Recent research has indicated that the uterine lining, or endometrium, is a rich source of adult stem cells. But retrieving those cells is as invasive as harvesting adult stem cells from other sources, such as bone marrow.
Now two separate groups say they have found these endometrial stem cells in menstrual blood.
Both groups say the cells in question show all the hallmarks of stem cells: they replicate themselves without differentiating, they can be made to differentiate into many different cell types under the right conditions, and they show characteristic cell surfaces of stem cells.
Xiaolong Meng of
the Bio-Communications Research Institute, a private research institute in Witchita, Kansas, US, and his colleagues studied cells taken from menstrual blood from two women.
The researchers say they found cells that proliferated more rapidly than mesenchymal stem cells derived from umbilical cords, doubling about every 19.4 hours. They also showed classic adult stem cell markers, as well as a few embryonic stem cell markers, such as one “master” marker called Oct-4.
The researchers also found that their cells could be coaxed into differentiating into nine different types of cells, including fat, muscle, bone and nerve.
Julie Allickson, chief scientist at Cryo-Cell International, the world’s biggest cord blood bank, based in Oldsmar, Florida, US, has also found stem cells in menstrual blood, although the work remains unpublished. Like Meng, she says the cells are highly proliferative, differentiate into at least five separate lineages and express stem cell markers.
What is more, Cryo-Cell has patented a collection, processing and freeze-storage technique, called “C’Elle”, which enables women to preserve their own menstrual stem cells. Although at this point the stored cells are intended for use by only the woman herself, there is speculation that the cells may help others as well. “There are indicators that they could be used for first or second degree relatives, or beyond,” says Allickson.
Caroline Gargett, of Monash University in Victoria, Australia, who first identified endometrial stem cells in the uterine lining, admits she is a little surprised. “I’d always thought the body wouldn’t want to be shedding too many stem cells,” she says. Both sets of findings are “very interesting and very significant”, she says.
Cryo-cell has partnered with four outside stem-cell researchers to examine potential use of the cells in treating heart disease, diabetes, and spinal cord injury. Meng’s group is also investigating the cells’ use in diabetes.
[Journal reference: Journal of Translational Medicine (DOI: 10.1186/1479-5876-5-57); 15 November 2007, NewScientist.com news service, by Alison Motluk]
The cells which thicken the womb wall during a woman's menstrual cycle contain a newly discovered type of stem cell, and could be used in the treatment of damaged and/or old tissue, according to research published today in the online open access publication, Journal of Translational Medicine.
Dr. Xiaolong Meng of the Bio-Communications Research Institute in Wichita, Kansas, led the research team consisting of scientists from the University of Alberta, University of Western Ontario and Medistem Laboratories (mdsm.ob). The team identified a new type of stem cell that can be reproducibly isolated from menstrual blood collected from healthy female subjects.
"We have many problems with our current methods of stem cell therapy, like those taken from bone marrow," commented Dr Meng, "They may be rejected by the recipient and/or have limited potential to generate new tissue. Now we've found a possible new way to overcome these difficulties by using cells from menstrual blood."
The growth of new blood vessels from pre-existing blood vessels is an essential part of the uterine or womb phase of the menstrual cycle. Cells collected from the menstrual blood of women include types which can be cultured in the laboratory, which replicate almost 70 times in a very rapid time span. This replication rate is far faster than cells which are currently used, taken from umbilical cord blood and bone marrow.
The cells are so unique in their ability to develop into at least 9 different cells including heart, liver and lung, that researchers called the cells Endometrial Regenerative Cells (ERC).
Not only do ERC replicate at a phenomenal rate of almost every 20 hours, but they produce unique growth factors at a rate of almost 100,000 greater than cells from umbilical cord blood.
A mere 5ml of menstrual blood collected from a healthy woman provided enough cells which after two weeks of culture provided beating heart cells.
The results of this breakthrough research indicate that these cells could be cultured at a large scale, thereby providing an alternative to the current methods of using bone marrow and umbilical cord blood, which itself poses threats of rejection.