Researchers know that one’s circulating blood contains one’s own stem cells. How many exactly is still not exactly clear. But more and more studies are coming out about using these circulating stem cells to revive dying or dead tissue.
Both Platelet Rich Plasma and Autologous Serum have circulating stem cells but the exact quantity is not clear. Still these circulating stem cells likely play a roll, in addition to the growth factors present in PRP and AS in helping patients improve in dry eye symptoms and likely in the meibomian gland dysfunction.
Exciting!
Sandra Lora Cremers, MD, FACS
References:
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Research Highlights
Nature Reports Stem Cells
Published online: 20 December 2007 | doi:10.1038/stemcells.2007.131
Published online: 20 December 2007 | doi:10.1038/stemcells.2007.131
Circulating stem cells
Simone Alves1
Haematopoietic stem cells patrol the body to ward off infection
Haematopoietic stem and progenitor cells (HSPCs) do not merely generate the immune system but take an active part in its actions. “Stem cells are more adventurous than we expected,” says Ulrich von Andrian of the Harvard Medical School in Cambridge, Massachusetts who recently reported his findings in Cell.1 Far from staying put in their bone-marrow niche, small numbers of HSPCs are continually circulating throughout the body and if required, can remain in an infected tissue and quickly produce cells needed to fight the infection.
Most blood cells have relatively short life spans and are regularly replenished from HSPCs in the bone marrow. These progenitors are not restricted to the bone marrow, however, but are known to migrate from it into the blood and have previously been found in other organs, including liver, lungs and kidneys. The new work examines what happens to HSPCs that leave the bone marrow, showing that they circulate from bone marrow to tissues and back to the blood via lymph. The team also shows that HSPCs potentially have the capacity to migrate specifically into sites of infection and differentiate there to replenish local supplies of white blood cells, especially dendritic cells.
The researchers first investigated lymph, the extracellular fluid that drains from tissues and circulates via the lymphatic system to re-enter the bloodstream via the thoracic duct. The researchers found that thoracic duct lymph from mice contains a small number of HSPCs. Experiments with a variety of genetically engineered mice then showed that these lymph-borne HSPCs are indeed derived from bone marrow and have the potential to develop into white blood cells of the myeloid lineage and into T lymphocytes. The pluripotent nature of these HSPCs in vivo was confirmed by their ability to partly reconstitute the mouse haematopoietic system. From all these experiments, the researchers established that HSPCs leaving the bone marrow travel in the blood to peripheral organs such as the spleen, lungs, liver and kidneys and remain there for at least 36 hours before draining into the lymphatic system, from which they are returned to the blood and eventually to the bone marrow. This circulation route suggests that these HSPCs might be actively involved in surveying tissues for signs of infection.
Further experiments supported this theory by showing that the HSPCs can detect a common bacterial component, bacterial lipopolysaccharide (LPS). In response, HSPCs enter the infected tissues and rapidly proliferate and differentiate there into a variety of white blood cells of the myeloid lineage, especially the antigen-presenting dendritic cells, thus replenishing these cells locally when they are needed. In addition, the group found that the presence of the toxin acts to retain the HSPCs in the tissues. The normal exit of HSPCs from organs into the lymphatic system is controlled by a lipid signal. But once the cells encounter LPS, the tissue-exit signal is blocked, retaining them in the infected tissue.
It is too early to tell what the clinical relevance of this work will be, but the group hopes to start examining how the trafficking pattern of HSPCs is correlated with pathological conditions.
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Reference
Author affiliation
- Simone Alves is an intern with Nature Publishing Group in London.
2.
Published online 5 August 2010 | Nature | doi:10.1038/news.2010.394
News
Skin cells converted to heart muscle cells
Cell identity switched in mice without the use of stem cells.
If generating heart muscle cells from other adult cells works in humans as well as mice, it could be a boon for the millions with heart failure.IStockphoto
By simply switching on three critical genes, researchers have coaxed mouse skin cells into becoming heart muscle cells — without their first reverting back to an embryonic, stem-cell-like state.
If the technique works in humans, it could provide a source of new heart muscle for the millions of people who develop heart failure each year. It is also the latest example of a process called ‘transdifferentiation’, in which adult cells take on an entirely different identity.
Even as labs around the world rush to perfect the latest stem-cell technologies, increasing numbers are trying to manipulate cell identity without using stem cells at all. The technique could allow researchers to avoid some difficulties associated with stem-cell therapies, including the potential to seed cancer, and the difficulty of coaxing stem cells to take on a particular cellular identity.
“I don’t know that this will entirely replace stem cells,” says Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease in San Francisco, California, and lead author on the study, published today in Cell1. “But it will offer another strategy that might remove some of the concerns of using stem cells.”
End of the line
Once it is damaged, heart muscle cannot repair itself. Increasing damage over time weakens the heart, eventually causing it to fail. In the United States, 5 million patients have heart failure, but only 2,000 heart transplants are performed each year.
Srivastava and his colleagues have previously tried to use stem cells to generate heart muscle cells. But their attempts failed, he says, because the heart muscle cells they made stalled in an immature state: although the cells contracted spontaneously — a hallmark of cardiac muscle cells — their contractions were not as strong as those of mature heart muscle cells.
So his team decided to try a different approach. They searched for genes that are expressed at high levels in heart muscle cells, and then narrowed the list down to three that were sufficient to convert another type of heart cell, structural cells called cardiac fibroblasts, into heart muscle cells.
Activating those three genes was sufficient to convert the cardiac fibroblasts or similar cells in skin to heart muscle cells. When implanted into mouse hearts, the cells made from cardiac fibroblasts contracted normally.
The results raise the possibility that a similar approach could be used to convert cardiac fibroblasts already in the heart to muscle cells, without the need for cell transplants, says Srivastava. His team is now investigating whether the same three genes are enough to switch cell identity in humans.
Identity crisis
Srivastava’s work represents major progress in a field with a chequered past, says George Daley, a stem-cell biologist at the Children’s Hospital Boston in Massachusetts. About 10 years ago, reports emerged from several labs that bone-marrow cells had been converted to many other cell types. This later turned out to be an experimental artefact: instead of taking on a new identity, the bone-marrow cells had simply fused to other types of cells.
After that, says Daley, the tide turned against transdifferentiation. In fact, researchers in the field shy away from that label altogether, says Marius Wernig, a stem-cell researcher at Stanford University in California. In January, Wernig and his colleagues reported the conversion of fibroblasts into neurons, a process that he calls “direct conversion” rather than transdifferentiation2.
But in 2006, Shinya Yamanaka, a stem-cell researcher at Kyoto University in Japan, reported that he could convert fibroblasts into a new kind of stem cell, called ‘induced pluripotent stem cells’, by simply switching on four genes. The finding convinced Wernig and others in the field that there was hope for transdifferentiation after all.
Since then, the field has picked up steam. Daley estimates that there are more than a hundred labs now racing to directly convert cells from one identity to another. Earlier this year, Wernig’s research prompted stem-cell biologists Cory Nicholas and Arnold Kriegstein of the University of California, San Francisco, to write: “Such are the developments in cell transdifferentiation that one might ask if stem cells will be dispensable in the quest for regenerative medicine3.”
More to learn
But Wernig hesitates to dismiss stem cells just yet. “It is still very early in the direct conversion field,” he says. “Probably there will be applications where stem cells have advantages.” In particular, Wernig notes, stem cells proliferate well and therefore may be more useful when large quantities of cells are needed.
Daley, meanwhile, says the field still needs to learn more about transdifferentiated cells. “There’s a lot of speculation right now,” he explains.
Daley and his colleagues recently reported that induced pluripotent stem cells bear what Daley calls “significant memories of their former lives” in the form of characteristic DNA modifications that can affect gene expression4. Although Srivastava’s team looked for such modifications near some genes, they have not yet performed a genome-wide scan.
“If, in fact, these transdetermined cells carry more of this memory of their tissue of origin, it does make you worry,” says Daley. Such a finding could limit the flexibility of the technique, he notes, forcing researchers to minimize these differences by interconverting only closely related cells.
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References
- Ieda, M. et al. Cell 142, 375-386 (2010).
- Vierbuchen, T. et al. Nature 463, 1035-1041 (2010).
- Nicholas, C. R. & Kriegstein, A. R. Nature 463, 1031-1032 (2010).
- Kim, K. et al. Nature doi:10.1038/nature09342 (2010).
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NATURE | NEWS
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Lab-grown blood stem cells produced at last
Two research teams cook up recipe to make long-sought cells in mice and people.
After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described today in Nature1, 2, offers hope to people with leukaemia and other blood disorders who need bone-marrow transplants but can’t find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.
One team, led by stem-cell biologist George Daley of Boston Children’s Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature1. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells2.
“For many years, people have figured out parts of this recipe, but they’ve never quite gotten there,” says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. “This is the first time researchers have checked all the boxes and made blood stem cells.”
Daley’s team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells into induced pluripotent stem (iPS) cells, which are capable of producing many other cell types. Until now, however, iPS cells have not been morphed into cells that create blood.
The next step was the novel one: Daley and his colleagues inserted seven transcription factors — genes that control other genes — into the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are “tantalizingly close” to naturally occurring ‘haemopoetic’ blood stem cells, says Daley.
Bhatia agrees. “It’s pretty convincing that George has figured out how to cook up human haemopoetic stem cells,” he says. “That is the holy grail.”
Bloody good
By contrast, Rafii’s team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.
When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full life — more than 1.5 years in the lab.
Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daley’s procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.
But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafii’s method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.
Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells. “A lot of people have become jaded, saying that these cells don’t exist in nature and you can’t just push them into becoming anything else,” Bhatia says. “I hoped the critics were wrong, and now I know they were.”
- Nature
- doi:10.1038/nature.2017.22000