Category Archives: Stem Cells

A stem cell capable of regenerating both bone and cartilage has been identified in bone marrow of mice. The discovery by researchers at Columbia University Medical Center (CUMC) is reported today in the online issue of the journal Cell.

The cells, called osteochondroreticular (OCR) stem cells, were discovered by tracking a protein expressed by the cells. Using this marker, the researchers found that OCR cells self-renew and generate key bone and cartilage cells, including osteoblasts and chondrocytes. Researchers also showed that OCR stem cells, when transplanted to a fracture site, contribute to bone repair.

"We are now trying to figure out whether we can persuade these cells to specifically regenerate after injury. If you make a fracture in the mouse, these cells will come alive again, generate both bone and cartilage in the mouse--and repair the fracture. The question is, could this happen in humans," says Siddhartha Mukherjee, MD, PhD, assistant professor of medicine at CUMC and a senior author of the study.

The researchers believe that OCR stem cells will be found in human bone tissue, as mice and humans have similar bone biology. Further study could provide greater understanding of how to prevent and treat osteoporosis, osteoarthritis, or bone fractures.

"Our findings raise the possibility that drugs or other therapies can be developed to stimulate the production of OCR stem cells and improve the body's ability to repair bone injury--a process that declines significantly in old age," says Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at CUMC, who initiated this research. Previously, Dr. Wang found an analogous stem cell in the intestinal tract and observed that it was also abundant in the bone.

"These cells are particularly active during development, but they also increase in number in adulthood after bone injury," says Gerard Karsenty, MD, PhD, the Paul A. Marks Professor of Genetics and Development, chair of the Department of Genetics & Development, and a member of the research team.

The study also showed that the adult OCRs are distinct from mesenchymal stem cells (MSCs), which play a role in bone generation during development and adulthood. Researchers presumed that MSCs were the origin of all bone, cartilage, and fat, but recent studies have shown that these cells do not generate young bone and cartilage. The CUMC study suggests that OCR stem cells actually fill this function and that both OCR stems cells and MSCs contribute to bone maintenance and repair in adults.

The researchers also suspect that OCR cells may play a role in soft tissue cancers.

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The above story is based on materials provided by Columbia University Medical Center. Note: Materials may be edited for content and length.

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Bone stem cells shown to regenerate bones, cartilage in adult mice

VIDEO:A stem cell capable of regenerating both bone and cartilage has been identified in bone marrow of mice. The discovery by researchers at Columbia University Medical Center (CUMC) is reported... view more

NEW YORK, NY (January 15, 2015) - A stem cell capable of regenerating both bone and cartilage has been identified in bone marrow of mice. The discovery by researchers at Columbia University Medical Center (CUMC) is reported today in the online issue of the journal Cell.

The cells, called osteochondroreticular (OCR) stem cells, were discovered by tracking a protein expressed by the cells. Using this marker, the researchers found that OCR cells self-renew and generate key bone and cartilage cells, including osteoblasts and chondrocytes. Researchers also showed that OCR stem cells, when transplanted to a fracture site, contribute to bone repair.

"We are now trying to figure out whether we can persuade these cells to specifically regenerate after injury. If you make a fracture in the mouse, these cells will come alive again, generate both bone and cartilage in the mouse--and repair the fracture. The question is, could this happen in humans," says Siddhartha Mukherjee, MD, PhD, assistant professor of medicine at CUMC and a senior author of the study.

The researchers believe that OCR stem cells will be found in human bone tissue, as mice and humans have similar bone biology. Further study could provide greater understanding of how to prevent and treat osteoporosis, osteoarthritis, or bone fractures.

"Our findings raise the possibility that drugs or other therapies can be developed to stimulate the production of OCR stem cells and improve the body's ability to repair bone injury--a process that declines significantly in old age," says Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at CUMC, who initiated this research. Previously, Dr. Wang found an analogous stem cell in the intestinal tract and observed that it was also abundant in the bone.

"These cells are particularly active during development, but they also increase in number in adulthood after bone injury," says Gerard Karsenty, MD, PhD, the Paul A. Marks Professor of Genetics and Development, chair of the Department of Genetics & Development, and a member of the research team.

The study also showed that the adult OCRs are distinct from mesenchymal stem cells (MSCs), which play a role in bone generation during development and adulthood. Researchers presumed that MSCs were the origin of all bone, cartilage, and fat, but recent studies have shown that these cells do not generate young bone and cartilage. The CUMC study suggests that OCR stem cells actually fill this function and that both OCR stems cells and MSCs contribute to bone maintenance and repair in adults.

The researchers also suspect that OCR cells may play a role in soft tissue cancers.

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Bone stem cells shown to regenerate bone and cartilage in adult mice

Japanese research also report the stem cells have effect on natural killer cells and monocyte function

Putnam Valley, NY. (Jan. 16th, 2015) - Stem cells derived from human amnion have for some time been considered promising for cell therapies because of their ease of access, ability to differentiate, and absence of ethical issues. Now, a Japanese research team has found that stem cells derived from human female amnion also have immunosuppressive activity and that the addition of antibodies to specific factors can enhance their immunosuppressive potential.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1273_Li_et_al.

The amniotic membrane is a tissue of fetal origin comprised of three layers. It is thought that there is a special immunologic mechanism protecting the fetus, so researchers were interested in finding out what immunological properties might reside in - and be extractable from - amnion cells.

"The human amniotic membrane contains both epithelial cells and mesenchymal cells," said study co-author Dr. Toshio Nikaido, Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences at the University of Toyama, Toyoma, Japan. "Both kinds of cells have proliferation and differentiation characteristics, making the amniotic membrane a promising and attractive source for amnion-derived cells for transplantation in regenerative medicine. It is clear that these cells have promise, although the mechanism of their immune modulation remains to be elucidated."

In this study, amnion-derived cells exerted an inhibitory effect on natural killer cells (NKs) and induced white blood cell activation. The researchers reported that the amnion-derived cells saw increases in interleukin-10 (IL-10).

"We consider that IL-10 was involved in the function of amnion-derived cells toward NK cells," explained Dr. Nikaido. "The immunomodulation of amnion-derived cells is a complicated procedure involving many factors, among which IL-10 and prostaglandin E2 (PGE2) play important roles."

Naturally occurring prostaglandins, such as PGE2, have important effects in labor and also stimulate osteoblasts to release factors that stimulate bone resorption by osteoclasts. PGE2 also suppresses T cell receptor signaling and may play a role in resolution of inflammation.

The use of antibodies against PGE2 and IL-10 removed the immunosuppressive effects of the amnion-derived cells by increasing natural killer cell cytotoxicity. This implies that these two factors are contributing elements to the immunosuppressive abilities of amnion-derived cells.

"Soluble factors IL-10 and PGE2 produced by amnion-derived cells may suppress allogenic, or "other" related immune responses," concluded Dr. Nikaido. "Our findings support the hypothesis that these cells have potential therapeutic use. However, further study is needed to identify the detailed mechanisms responsible for their immodulatory effects. Amnion-derived cells must be transplanted into mouse models for further in vivo analysis of their immunosuppressive activity or anti-inflammatory effects."

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Stem cells derived from amniotic tissues have immunosuppressive properties

New York, Jan 16 (IANS): Indian-American researcher Siddhartha Mukherjee from Columbia University Medical Center (CUMC) has identified stem cells that are capable of regenerating both bone and cartilage in bone marrow of mice.

The cells called osteochondroreticular (OCR) stem cells were discovered by tracking a protein expressed by the cells.

Using this marker, Mukherjee and his team found that OCR cells self-renew and generate key bone and cartilage cells.

The team also showed that OCR stem cells, when transplanted to a fracture site, contribute to bone repair.

The researchers believe OCR stem cells are present in human bone tissue as mice and humans have similar bone biology.

"If you make a fracture in the mouse, these cells will come alive again, generate both bone and cartilage in the mouse and repair the fracture. The question is, could this happen in humans," asked Mukherjee, assistant professor of medicine.

Further study could provide greater understanding of how to prevent and treat osteoporosis, osteoarthritis or bone fractures.

The researchers also suspect that OCR cells may play a role in soft tissue cancers.

The paper was reported online in the journal Cell.

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Bone stem cells may regenerate bones and cartilage

Osteoarthritis is a common condition seen in older people in which the tissue between joints becomes worn down, causing severe pain. In what could be an important development for people who suffer from it, U.S. researchers have isolated stem cells in adult mice that regenerate both worn tissue, or cartilage, and bone.

For the past decade, researchers have been trying to locate and isolate stem cells in the spongy tissue or marrow of bones of experimental animals.

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The so-called osteochondroreticular, or OCR, cells are capable of renewing and generating important bone and cartilage cells.

Researchers at Columbia University Medical Center in New York identified these master cells in the marrow. When grown in the lab and transplanted back into a fracture site in mice, they helped repair the broken bones.

Siddhartha Mukherjee, the study's senior author, said similar stem cells exist in the human skeletal system.

The real provocative experiment or the provocative idea is being able to do this in humans being able to extract out these stem cells from humans and being able to put them back in to repair complex fracture defects or osteoarthritis defects, said Mukherjee.

He noted that children have more bone stem cells than adults, which may explain why the bones of young people repair more easily than fractures in adults.

Mukherjee said the next step is to try to identify the OCR cells in humans and attempt to use them to repair complex bone and cartilage injuries.

Once cartilage is injured or destroyed in older people, as in osteoarthritis, Mukherjee said it does not repair itself.

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Bone Stem Cells Regenerate Bone, Cartilage in Mice

FRESNO, Calif. (KFSN) --

Our bodies contain 23 pairs of them, 46 total. But if chromosomesare damaged, they can cause birth defects, disabilities, growth problems, even death.

Case Western scientist Anthony Wynshaw-Boris is studying how to repair damaged chromosomes with the help of a recent discovery. He's taking skin cells and reprogramming them to work like embryonic stem cells, which can grow into different cell types.

"You're taking adult or a child's skin cells. You're not causing any loss of an embryo, and you're taking those skin cells to make a stem cell." Anthony Wynshaw-Boris, M.D., PhD, of Case Western Reserve University, School of Medicine told ABC30.

Scientists studied patients with a specific defective chromosome that was shaped like a ring. They took the patients' skin cells andreprogrammed them into embryonic-like cells in the lab. They found this process caused the damaged "ring" chromosomes to be replaced by normal chromosomes.

"It at least raises the possibility that ring chromosomes will be lost in stem cells," said Dr. Wynshaw-Boris.

While this research was only conducted in lab cultures on the rare ring-shaped chromosomes, scientists hope it will work in patients with common abnormalities like Down syndrome.

"What we're hoping happens is we might be able to use, modify, what we did, to rescue cell lines from any patient that has any severe chromosome defect," Dr. Wynshaw-Boris explained.

It's research that could one day repair faulty chromosomes and stop genetic diseases in their tracks.

The reprogramming technique that transforms skin cells to stem cells was so ground-breaking that a Japanese physician won the Nobel Prize in medicine in 2012 for developing it.

More:
Stem Cells to Repair Broken Chromosomes: Medicine's Next Big Thing?

A new technique to image messenger RNA activity in real time has been developed by researchers at the National Institutes of Health in Maryland in the US and Xidian University in Shaanxi, China. The technique, which was used in this work to track how mRNA expresses itself in neuronal stem cells as they differentiate, could help us better understand neurogenesis and perhaps even be used to screen drugs for treating neurodegenerative diseases and brain trauma.

Messenger ribonucleic acid (mRNA) is the form of RNA that helps transfer genetic information from inside the cell nucleus to ribosomes in the cytoplasm. It acts as a template for making proteins and is synthesized from a DNA template during a process known as transcription. When mRNA dynamics are disrupted, pathological abnormalities such as interrupted embryonic development and cell death can occur.

Imaging mRNA in real time is no easy task and most techniques that have attempted to do this to date have failed. A team led by Shawn Chen of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health says that it has now designed a new nanocomplex containing multiple mRNA imaging probes that can retrieve spatial and temporal information from different mRNA sequences.

We used gold nanoparticles as the core of our nanocomplex, explains team member Zhe Wang of the School of Life Sciences and Technology at Xidian University and the National Institutes of Health. This core is functionalized with a dense layer of stable dithiol-modified DNA oligonucleotides hybridized with distinctive fluorophore-capped reporter sequences.

The fluorophore attached to the reporter sequences does not fluoresce when it is attached to the gold nanoparticle core (it is quenched), but it reactivates when it attaches to mRNA. The mRNA competitively hybridizes with the DNA oligonucleotides on the nanocomplex, and it is more attracted to this DNA than are the existing reporter genes.

The technique allows for real-time imaging of mRNA without any artifacts, Chen tells nanotechweb.org. The nanocomplex is also very stable in the cell cytosol, is resistant to endonuclease enzymes that might otherwise break it down, and senses mRNA fast.

By using the nanocomplex in conjunction with computer programme codes and imaging software, the researchers were able to follow how mRNA expresses itself during neural stem cell differentiation. This differentiation plays a crucial role in both the developing and adult nervous system. The technique might thus be used as a chemical screening platform for treating neurodegenerative diseases, such as Alzheimers and Parkinsons, as well as brain trauma, explains Chen.

The team says that it is now busy improving its nanocomplex platform to explore small interfering RNA or micro RNA regulated neural stem cell differentiation and corresponding mRNA sequential expression imaging profiles. We are also trying to optimize this system and adapt it to various cell types, to ultimately create a versatile nanocomplex for use in a host of basic biology studies and chemical screening in regenerative medicine, says team member Zhongliang Wang, who works in China and the US.

The research is detailed in ACS Nano DOI: 10.1021/nn505047n.

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Nanocomplex images differentiating stem cells

6 hours ago by Amanda Morris

Electroporation is a powerful technique in molecular biology. By using an electrical pulse to create a temporary nanopore in a cell membrane, researchers can deliver chemicals, drugs, and DNA directly into a single cell.

But existing electroporation methods require high electric field strengths and for cells to be suspended in solution, which disrupts cellular pathways and creates a harsh environment for sensitive primary cells. This makes it nearly impossible for researchers to study the cells naturally, in a setting that encourages the cells to continue differentiating and expanding.

A Northwestern University collaboration has developed a novel microfluidic device that allows for electroporation of stem cells during differentiation, making it possible to deliver molecules during this pivotal time in a cell's life. This provides the conditions needed to study primary cells, such as neurons, opening doors for exploration of the pathogenic mechanisms of neural diseases and potentially leading to new gene therapies.

Developed by Horacio Espinosa, the James and Nancy Farley Professor of Manufacturing and Entrepreneurship at the McCormick School of Engineering, and John Kessler, the Ken and Ruth Davee Professor of Stem Cell Biology at the Feinberg School of Medicine, the localized electroporation device (LEPD) can be applied to adherent cells, which are grown on an artificial substrate as opposed to free-floating in a culture medium and are able to continue growing and differentiating.

"The ability to deliver molecules into adherent cells without disrupting differentiation is needed for biotechnology researchers to advance both fundamental knowledge and the state-of-the-art in stem cell research," Espinosa said.

"Non-destructive manipulation of cells over time and in the correct environment is a key enabling technology highly needed within the biology and medical research communities," Kessler said.

The research is described in a paper published in the September 10 issue of Lab on a Chip, the journal of The Royal Society of Chemistry, and was also highlighted on the journal's back cover.

Explore further: Stem cells born out of indecision

(Phys.org) Northwestern University researchers have developed a new method for delivering molecules into single, targeted cells through temporary holes in the cell surface. The technique could find applications ...

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New device allows for manipulation of differentiating stem cells

Stem cell technology representsone of the most fascinating and controversial medical advances of the past several decades. By now the enormous controversy which surrounded the use of federal funds to conduct scientific research on human stem cells during the George W. Bush administration has largely blown over. Five years have passed since President Obama lifted federal funding restrictions, and amazing progress has already been made in the field.

One can make a good case for stem cells being the most fascinating and versatile cells in the human body. This is precisely due to their stem role. In their most basic form, theyre capable of both replicating themselves an unlimited number of times and differentiating themselvesinto a huge number of other cell types. Muscle cells, brain cells, organ cells, and many others can all be created from stem cells. If youre interested, the NIH has an awesome introductionon stem cells on their website.

The question which has arisen since the discovery of thisamazing cell type has been how to harness their power and versatility. This is the primary focus of research today: how can we precisely control stem cells to perform whatever tasks we need them to do? Of course, other important issues, such as figuring out thebest places from which to harvest stem cells,exist.

Because of their role in the body, the number of potential applications for stem cells are truly stunning. From building custom cell clusters with 3D printers to curing a variety of diseases through bone marrow transplants, growingorgans for transplants, andeven growing edible meat, research is progressing at a frantic pace.

There are two particular areas of research which seem to hold the greatest promise at this point. The first is organs. Anyone who has ever been involved in an organ transplant knows how incredibly complex and difficult the process is. But difficulties like finding the right donor, preserving the organ, and finding enough supply to meet the incredible demand could all be overcome if we could simply use stem cells to grow a custom organ for each transplant from scratch.

Besides this perhaps science-fiction-sounding process of growing organs, theres also incredible excitement surrounding the potential of bone marrow transplants to cure diseases like HIVand Leukemia. This is done by implanting stem cells containing genetic mutations which confer immunity to a variety of diseases into a patients bone marrow, where they can begin naturally replicating and affecting the immune system.

Thisprocedurealso covers transplants designed simply to reintroduce healthy stem cells to help tackle a wider variety of ailments. Often, referred to as regenerative medicine as itinvolves stimulating the bodys preexisting repair mechanisms to help the healing process,thisprocedurealso offer great promise.

Naturally, the speed at which advances are being made in the field has led to problems as well. One recent well-publicized study which seemed to point to the possibility of achieving stimulus-triggered acquisition of pluripotency (essentially demonstrating a new type of stem cells) is now believedto have beenfraudulent.

More:
The Future of Stem Cells: Opportunities at the Cutting Edge of Science

Novel cancer stem cells glioma cell invasion - Dr Paul Brennan
Dr Paul Brennan, University of Edinburgh, talks about his research into the identification of a novel cancer stem cell that might be important for glioma cel...

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Novel cancer stem cells & glioma cell invasion - Dr Paul Brennan - Video