Category Archives: Stem Cells

Understanding Niche Cells | Science: Out of the Box
Johns Hopkins cell biologist Erika Matunis explains how understanding the cells that take care of stem cells may shed light on cancer. To see more Science: Out of the Box videos, visit http://www...

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New York, Oct 20 (IANS): Megakaryocytes or large cells found in bone marrow play a critical role in regulating stem cells, found a study.

In fact, haematopoietic stem cells differentiate to generate megakaryocytes in bone marrow. The study is the first to show that haematopoietic stem cells (the parent cells) can be directly controlled by their own progeny (megakaryocytes).

The results could lead to new treatments for patients recovering from chemotherapy or organ transplantation.

"Our results suggest that megakaryocytes might be used clinically to facilitate adult stem cell regeneration and to expand cultured cells for adult stem cell transplants," said lead author of the study Meng Zhao from the Stowers Institute for Medical Research in Missouri, US.

The researchers found that megakaryocytes directly regulate the function of murine (mice) haematopoietic stem cells - adult stem cells that form blood and immune cells and that constantly renew the body's blood supply.

These cells can also develop into different types of blood cells, including white blood cells, red blood cells and platelets.

The researchers discovered that as a terminally differentiated progeny, megakaryocytes regulate haematopoietic stem cells by performing two previously unknown functions.

"Megakaryocytes can directly regulate the amount of haematopoietic stem cells by telling the cells when they need to keep themselves in the quiescent stage and when they need to start proliferating to meet an increased demand," Zhao concluded.

The study appeared in the journal Nature Medicine.

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Parent stem cells controlled by progeny

While megakaryocytes are best known for producing platelets that heal wounds, these "mega" cells found in bone marrow also play a critical role in regulating stem cells according to new research from the Stowers Institute for Medical Research. In fact, hematopoietic stem cells differentiate to generate megakaryocytes in bone marrow. The Stowers study is the first to show that hematopoietic stem cells (the parent cells) can be directly controlled by their own progeny (megakaryocytes).

The findings from the lab of Stowers Investigator Linheng Li, Ph.D., described in the Oct. 19 issue of the journal Nature Medicine, could cause researchers to rethink what they know about the workings of megakaryocytes and potentially lead to new treatments for patients recovering from chemotherapy or organ transplantation.

"Our results suggest that megakaryocytes might be used clinically to facilitate adult stem cell regeneration and to expand cultured cells for adult stem cell transplants," says Meng Zhao, Ph.D., a postdoctoral fellow at Stowers and lead author on the study. Stowers researchers discovered that megakaryocytes directly regulate the function of murine hematopoietic stem cells -- adult stem cells that form blood and immune cells and that constantly renew the body's blood supply. These cells can also develop into all types of blood cells, including white blood cells, red blood cells, and platelets.

Because of their remarkable ability to renew themselves and differentiate into other cells, hematopoietic stems cells are the focus of intense research and have been used to treat many diseases and conditions. The transplantation of isolated human hematopoietic stem cells is used in the treatment of anemia, immune deficiencies and other diseases, including cancer.

Basic research has centered on identifying and characterizing hematopoietic stem cells, however, it is still not clear how hematopoietic stem cells actually work, and how they are regulated because of the complexity of the bone marrow microenvironment. Zhao and his colleagues discovered that as a terminally differentiated progeny, megakaryocytes regulate hematopoietic stem cells by performing two previously unknown functions.

"Megakaryocytes can directly regulate the amount of hematopoietic stem cells by telling the cells when they need to keep in the quiescent stage, and when they need to start proliferating to meet increased demand." Maintaining that delicate balance is important, he adds. "You don't want to have too many or too few hematopoietic stem cells."

These findings are supported by similar research from the laboratory of Paul S. Frenette, Ph.D., at the Albert Einstein College of Medicine, also reported in the Oct. 19 issue of Nature Medicine.

Employing the advanced technology of the Institute's Cytometry, Imaging and Histology centers, the researchers examined the relationship between megakaryocytes and hematopoietic stem cells in mouse bone marrow. In the course of their research, they found that the protein transforming growth factor B1 (TGF-B1), contained in megakaryocytes, signaled quiescence of hematopoietic stem cells. They also found that when under stress from chemotherapy, megakaryocytes signaled fibroblast growth factor 1 (FGF1), to stimulate the proliferation of hematopoietic stem cells.

"Our findings suggest that megakaryocytes are required for the recovery of hematopoietic stem cells post chemotherapy," explains Li. The discovery could provide insight for using megakaryocyte-derived factors, such as TGF-B1 and FGF1, clinically to facilitate regeneration of hematopoietic stem cells, he adds.

Engineering a megakaryocyte niche (a special environment in which stem cells live and renew) that supports the growth of hematopoietic stem cells in culture, is the next step for the researchers. Zhao and his colleagues are also investigating whether a megakaryocyte niche can be used to help expand human hematopoietic stem cells in vitro and stem cell transplantation for patients.

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'Mega' cells control growth of blood-producing cells

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Newswise Kansas City, Mo. - While megakaryocytes are best known for producing platelets that heal wounds, these mega cells found in bone marrow also play a critical role in regulating stem cells according to new research from the Stowers Institute for Medical Research. In fact, hematopoietic stem cells differentiate to generate megakaryocytes in bone marrow. The Stowers study is the first to show that hematopoietic stem cells (the parent cells) can be directly controlled by their own progeny (megakaryocytes).

The findings from the lab of Stowers Investigator Linheng Li, Ph.D., described in the Oct. 19 issue of the journal Nature Medicine, could cause researchers to rethink what they know about the workings of megakaryocytes and potentially lead to new treatments for patients recovering from chemotherapy or organ transplantation.

Our results suggest that megakaryocytes might be used clinically to facilitate adult stem cell regeneration and to expand cultured cells for adult stem cell transplants, says Meng Zhao, Ph.D., a postdoctoral fellow at Stowers and lead author on the study. Stowers researchers discovered that megakaryocytes directly regulate the function of murine hematopoietic stem cellsadult stem cells that form blood and immune cells and that constantly renew the bodys blood supply. These cells can also develop into all types of blood cells, including white blood cells, red blood cells, and platelets.

Because of their remarkable ability to renew themselves and differentiate into other cells, hematopoietic stems cells are the focus of intense research and have been used to treat many diseases and conditions. The transplantation of isolated human hematopoietic stem cells is used in the treatment of anemia, immune deficiencies and other diseases, including cancer.

Basic research has centered on identifying and characterizing hematopoietic stem cells, however, it is still not clear how hematopoietic stem cells actually work, and how they are regulated because of the complexity of the bone marrow microenvironment. Zhao and his colleagues discovered that as a terminally differentiated progeny, megakaryocytes regulate hematopoietic stem cells by performing two previously unknown functions.

Megakaryocytes can directly regulate the amount of hematopoietic stem cells by telling the cells when they need to keep in the quiescent stage, and when they need to start proliferating to meet increased demand. Maintaining that delicate balance is important, he adds. You dont want to have too many or too few hematopoietic stem cells.

These findings are supported by similar research from the laboratory of Paul S. Frenette, Ph.D., at the Albert Einstein College of Medicine, also reported in the Oct. 19 issue of Nature Medicine.

Employing the advanced technology of the Institutes Cytometry, Imaging and Histology centers, the researchers examined the relationship between megakaryocytes and hematopoietic stem cells in mouse bone marrow. In the course of their research, they found that the protein transforming growth factor B1 (TGF-B1), contained in megakaryocytes, signaled quiescence of hematopoietic stem cells. They also found that when under stress from chemotherapy, megakaryocytes signaled fibroblast growth factor 1 (FGF1), to stimulate the proliferation of hematopoietic stem cells.

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New Insight That "Mega" Cells Control the Growth of Blood-Producing Cells

16.10.2014 - (idw) Max-Delbrck-Centrum fr Molekulare Medizin (MDC) Berlin-Buch

In their search for the earliest possible stage of development of human embryonic stem cells (hESCs) that still have the potential to develop into any types of body cells and tissue, researchers from the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, and the University of Bath, United Kingdom, have apparently been successful. Jichang Wang, Gangcai Xie, and Dr. Zsuzsanna Izsvk (MDC), together with Professor Laurence D. Hurst (University of Bath), report the discovery of a subtype of cells in culture dishes with hESCs and human induced pluripotent stem cells (hiPSCs) that resemble this very early, pluripotent or nave state (Nature, doi:10.1038/nature13804)*. They also discovered the mechanism that turns human ES cells into nave-like human stem cells. While this has potential implications for medicine and for understanding early human development, an evolutionary enigma still remains unsolved.

Human embryonic stem cells (hESCs) differ considerably from those of mice. Mouse nave cultures resemble the inner cell mass which gives rise to the embryo, while none of the cultured hESC lines do. Nave ESCs of mice are easy to maintain, but not human ESCs isolated from pre-implantation embryos. The hESC lines, researchers work with in their laboratories are considered to be less nave, and have limited differentiation potential. Researchers hypothesize that they have partially lost their pluripotency. Why this is so remains unclear.

What properties characterize human nave stem cells? Can they be identified and proliferated in the laboratory and retained in culture? Researchers in Europe, Asia and the USA are trying to find the answers to these questions in order to be able to use these cells for therapy in the future.

Evolution pointed the way It was evolution that showed the researchers in Bath and Berlin the way to the successful approach. They pinpointed one particular class of ancient viruses called HERVH (human endogenous retrovirus H). HERVH integrated into our DNA millions of years ago, and although it does not function as a virus any longer, it is not silent.

HERVH-derived sequences appear at a very early stage in human embryos, that is, HERVH is highly expressed at just the right time and place in human embryos where one would expect to see nave stem cells. This was also observed by Professor Kazutoshi Takahashi (Kyoto University, Kyoto, Japan), almost at the same time when Dr. Izsvk and Professor Hurst made their discovery.**

Dr. Izsvk and Professor Hurst succeeded in going one step further. They were able to identify the switch that regulates HERVH. In hESC cultures they identified a transcription factor called LBP9 as being central to the activity of HERVH in early embryos. Using a reporter system that made cells expressing HERVH via LBP9 glow green, the Berlin and Bath team found that they had purified human ESCs that showed all the hallmarks of nave mouse stem cells.

This transcription factor was not previously known to be important to human stem cells. However, unknown to them at the time, the same transcription factor was shown by Austin Smiths group (University of Cambridge, UK) to have a role in mouse nave cells***.

Our human nave-like cells look remarkably like the mouse ones, and are close to human inner cell mass (ICM), said Jichang Wang (PhD student, MDC), first author of the Nature publication. With our HERVH-based reporter system we can easily isolate nave-like human ESCs from any human ESC culture. These cells grow like the mouse nave stem cells and express many of the same genes such as NANOG, KLF4 and OCT4 that are associated with murine navet. When we knockdown LBP9 or HERVH, these cells no longer resemble nave-like human stem cells, he added.

To explore a potential role in stem cell-based therapeutics, the next task will be to keep these isolated human nave-like stem cells in culture and proliferate them. HERVH would also be particularly useful in identifying optimal conditions for long-term culturing. As HERVH inhibits differentiation, its expression should be transient, otherwise it might be detrimental to normal embryo development. What factors keep this delicate process in balance is yet to be determined.

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Researchers in Berlin and Bath Identify Nave-Like Human Stem Cells

Shassers Trials
Shassers Trials ...Outside Wormwood Scrubs Queen Charlottes Hospital ..after an unsuccessful appointment to discuss the stem cells that were implanted in me 30 years ago...letting off some...

By: Sharon Cooke

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Shassers Trials - Video

Whats the kindest thing a stranger #39;s done for you?
Every day at Anthony Nolan incredible people save the life of a stranger by donating their stem cells. That got us thinking, what #39;s the most amazing thing a stranger has done for you? ...

By: Anthony Nolan

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Whats the kindest thing a stranger's done for you? - Video

Stem cells from human skin and coaxed them into becoming fat, muscle and bone cells
Stem cells from human skin and coaxed them into becoming fat, muscle and bone cells. #39;Health Updates #39; connects health-conscious individuals with important ne...

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Stem cells from human skin and coaxed them into becoming fat, muscle and bone cells - Video

A HEALTHCARE worker at Royal Bournemouth Hospital has donated stem cells in a bid to save the life of an unknown man.

Claire Waugh, pictured, who has always been a regular blood donor, decided to join the Anthony Nolan stem cell register after her father was diagnosed with prostate cancer three years ago.

The healthcare assistant co-ordinator was later identified as a possible match for a man needing life-saving treatment.

Following rigorous testing Claire was visited by nurses from the blood cancer charity, who gave her three injections every day for three days to stimulate her bone marrow to produce stem cells.

On the fourth day she travelled to Kings College Hospital in London to receive a final set of injections and undergo a stem cell collection in a simple five-hour outpatient procedure, which is similar to giving blood.

Claire said: I couldnt move or bend my arm due to the fairly heavy duty needle, but I was looked after really well so in the end the time went very quickly.

After donating, Claires stem cells were rushed to the recipient within the required 72 hours. A volunteer from Anthony Nolan told me that if he doesnt survive, there is nothing else on this earth that would have cured him, so this was this persons last chance, added Claire.

When my dad was poorly it made me think that if he needed this kind of help, I would be praying every night that someone would help him.

By doing this, it meant that I could give that chance to someone else and their family.

Royal Bournemouth Hospital granted special leave to Claire for the donation with the charity covering all of her and her husbands travel expenses.

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My stem cells could help save the life of man Ive never met

Despite previous indications to the contrary, the esophagus does have its own pool of stem cells, said researchers from the University of Pittsburgh School of Medicine in an animal study published online today in Cell Reports. The findings could lead to new insights into the development and treatment of esophageal cancer and the precancerous condition known as Barrett's esophagus.

According to the American Cancer Society, more than 18,000 people will be diagnosed with esophageal cancer in the U.S. in 2014 and almost 15,500 people will die from it. In Barrett's esophagus, the lining of the esophagus changes for unknown reasons to resemble that of the intestine, though gastro-esophageal reflux disease or GERD is a risk factor for its development.

"The esophageal lining must renew regularly as cells slough off into the gastrointestinal tract," said senior investigator Eric Lagasse, Pharm.D., Ph.D., associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine. "To do that, cells in the deeper layers of the esophagus divide about twice a week to produce daughter cells that become the specialized cells of the lining. Until now, we haven't been able to determine whether all the cells in the deeper layers are the same or if there is a subpopulation of stem cells there."

The research team grew pieces or "organoids" of esophageal tissue from mouse samples, and then conducted experiments to identify and track the different cells in the basal layer of the tissue. They found a small population of cells that divide more slowly, are more primitive, can generate specialized or differentiated cells, and have the ability to self-renew, which is a defining trait of stem cells.

"It was thought that there were no stem cells in the esophagus because all the cells were dividing rather than resting or quiescent, which is more typical of stem cells," Dr. Lagasse noted. "Our findings reveal that there indeed are esophageal stem cells, and rather than being quiescent, they divide slowly compared to the rest of the deeper layer cells."

In future work, the researchers will examine human esophageal tissues for evidence of stem cell dysfunction in Barrett's esophagus disease.

"Some scientists have speculated that abnormalities of esophageal stem cells could be the origin of the tissue changes that occur in Barrett's disease," Dr. Lagasse said. "Our current and future studies could make it possible to test this long-standing hypothesis."

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The above story is based on materials provided by University of Pittsburgh Schools of the Health Sciences. Note: Materials may be edited for content and length.

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Stem cells discovered in the esophagus