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Newswise The Institute for Research in Immunology and Cancer (IRIC) at the Universit de Montral (UdeM), in collaboration with the Maisonneuve-Rosemont Hospitals Quebec Leukemia Cell Bank, recently achieved a significant breakthrough thanks to the laboratory growth of leukemic stem cells, which will speed up the development of new cancer drugs.

In a recent study published in Nature Methods, the scientists involved describe how they succeeded in identifying two new chemical compounds that allow to maintain leukemic stem cells in culture when these are grown outside the body.

This important advance opens the way to the identification of new cancer drugs to fight acute myeloid leukemia, one of the most aggressive forms of blood cancer.

The ability to grow leukemic stem cells in culture is a major breakthrough. The next step is to study the molecular mechanisms that regulate the survival and proliferation of leukemic cells as well as the resistance to cancer drugs.

This study is the work of the Leucgne research group. This group is co-directed by Dr. Guy Sauvageau, chief executive officer and principal investigator at IRIC as well as professor in the Department of Medicine at the UdeM; by Dr. Jose Hbert, director of the Quebec Leukemia Cell Bank, hematologist at Maisonneuve-Rosemont Hospital and professor in the Department of Medicine at the UdeM; and by Sbastien Lemieux, principal investigator at IRIC. The first author of the study is Caroline Pabst, a postdoctoral fellow at IRIC and associate of the Leucgne research group.

This research breakthrough demonstrates the advantage of working in a multidisciplinary team like the Leucgne research group, stated Drs. Sauvageau and Hbert. Access to cells of leukemia patients and to IRICs state-of-the-art facilities are also key factors in pursuing ground-breaking research.

Background to the study Stem cells located in the bone marrow are responsible for the production of blood cells. Unfortunately, deregulation of those cells often produces disastrous consequences when one of them develops mutations that transform it into a malignant cell called leukemic. The result is an abnormal proliferation of blood cells and the development of leukemia. Leukemic stem cells are also one of the likely causes of patient relapse because they are especially resistant to cancer treatments.

The major obstacle before this discovery was growing stem cells and keeping them intact in vitro, because they quickly lost their cancer stem cell character. As a result, it was very difficult to effectively study the multiplication of cells that cause leukemia.

More here:
Major Breakthrough in Developing New Cancer Drugs: Capturing Leukemic Stem Cells

FRESNO, Calif. (KFSN) -- Umbilical cord stem cell banking can be expensive and controversial, but Jamie and Ben Page decided to bank their daughter Harlow's stem cells, just in case. Then, "just in case" became a reality.

She spins, kicks, and giggles. Like most five year olds, Harlow Page is full of energy.

"This is Harlow when she was first born. We had heard about cord blood banking and talked about it a lot and thought let's just go for it and have it just as a backup," said Jamie Page, Harlow's mom.

It turns out they did need it. Harlow had cancer in her uterus.

"On the ultrasound they immediately saw that there was a mass in her abdomen about the size of a grapefruit," Jamie said.

After a year of chemo, the tumor was gone. Doctors wanted to keep it that way.

"So, when the doctors found out we actually had her own stem cells they were very excited," Jamie said.

"I think that her umbilical cord cells were used as a boost to her own cells when we harvested her to have adequate cells for reconstitution," said Elaine Morgan, MD, Oncologist, Lurie Children's Memorial Hospital.

Dr. Morgan does not advocate private cord stem cell banking at birth to be saved for a healthy baby's later use, because it's not clinically useful and it's expensive.

The Pages paid almost $2,000 for the initial banking fee, plus an extra $125 per year.

Read more:
The pros and cons of banking your baby's stem cells

17 hours ago by Bob Yirka Mesenchymal stem cell displaying typical ultrastructural characteristics. Credit: Robert M. Hunt/Wikipedia

(Phys.org) A team of researchers working at the University of Colorado has found that human stem cells appear to remember the physical nature of the structure they were grown on, after being moved to a different substrate. In their paper published in the journal Nature Materials, the researchers describe how they grew human stem cells on different substrates. In so doing, they discovered that the stem cells continued to express certain proteins related to a substrate even after its hardness was changed.

Scientists have known for some time that stem cells respond to their environment as they growthose grown on hard material, such as glass or metal for example, are more amenable to growing into bone cells. In this new effort, the researchers sought to discover if changes to a stem cell brought about by environment are retained if the stem cell is moved to a different environment.

To find out, the researchers used mesenchymal cells which are known to be able to grow into almost any human body part. They placed the stem cells on a stiff substrate then moved them to one less stiff over differing numbers of days. In so doing, they found that the longer the cells were left on the stiff substrate the more a protein connected to bone growth (RUNX2) was expressed. Conversely, cells that were first placed on a soft surface and subsequently moved to a hard surface demonstrated a tendency to develop either bone or adipogenic tendencies.

In another experiment, the researchers applied the stem cells to a substrate coated with a phototunable hydrogelit grows softer when exposed to lightusing it allowed for changing the stiffness of the substrate without having to move the cells. Using this approach the team found that if the cells were allowed to grow on the gel in its stiff state, for just one day, switching to a soft state caused the expression of RUNX2 to cease immediately. When they allowed the cells to grow for ten days on the stiff base, however, before switching to a soft one, expression of RUNX2 continued for another ten days before finally ceasing. This shows, the researchers contend, that stem cells have a memory component that is not yet understood.

The researchers note that their findings could be applied to other stem cell research areas such as cases where unintentional consequences may be arising in experiments due to the stiffness of the substrate in which they are being grown. It also raises the question of whether other environmental factors might be impacting cell growth and if so, if they have a memory component as well.

Explore further: Heart cells respond to stiff environments

More information: Mechanical memory and dosing influence stem cell fate, Nature Materials (2014) DOI: 10.1038/nmat3889

Abstract We investigated whether stem cells remember past physical signals and whether these can be exploited to dose cells mechanically. We found that the activation of the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) as well as the pre-osteogenic transcription factor RUNX2 in human mesenchymal stem cells (hMSCs) cultured on soft poly(ethylene glycol) (PEG) hydrogels (Young's modulus E ~ 2 kPa) depended on previous culture time on stiff tissue culture polystyrene (TCPS; E ~ 3 GPa). In addition, mechanical dosing of hMSCs cultured on initially stiff (E ~ 10 kPa) and then soft (E ~ 2 kPa) phototunable PEG hydrogels resulted in either reversible orabove a threshold mechanical doseirreversible activation of YAP/TAZ and RUNX2. We also found that increased mechanical dosing on supraphysiologically stiff TCPS biases hMSCs towards osteogenic differentiation. We conclude that stem cells possess mechanical memorywith YAP/TAZ acting as an intracellular mechanical rheostatthat stores information from past physical environments and influences the cells' fate.

Journal reference: Nature Materials

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Researchers find stem cells remember prior substrates

By Liisa Vexler

Scientists at the Children's Medical Center Research Institute, UT Southwestern Medical Center, Texas, have conducted a breakthrough piece of research into protein synthesis in adult stem cells. The research, previously not possible to conduct, has linked certain cancers with mutations affecting protein synthesis.

The process used an antibiotic called puromycin, in modified form, to aid in measuring the quantity of protein synthesized in the body. Research revealed that protein is produced at a different rate per hour for different types of blood cells. It was also noted that much lower amounts of protein are synthesized by stem cells than other cells (blood-forming). The research, conducted on mice, concluded that when ribosome, a genetic mutation involved in making protein, was present the production of protein in stem cells diminished by 30%. Conversely, in another experiment the tumor-suppressor gene P-ten was removed in an attempt to increase protein synthesis, resulting in an impairment of stem cell function. These findings conclude that protein synthesis for blood forming stem cells needs to be well regulated or else they will not function efficiently. A member of the team, Dr. Morrison, observed to his amazement that breeding Pten mutant mice with ribosomal mutant mice returned stem cell function to normal, leading to either a complete block or delay on the development of Leukaemia. Dr. Morrison is of the view that, all of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right. The findings are thought to open the door to a number of similar tests for the many kinds of cells in the human body, making it possible to study protein synthesis for each. The research is thought to be important for understanding the differences in the rates and ways that protein in synthesized in cells and what this means for cellular survival.

Continued here:
A Study of Protein Synthesis In Stem Cells Conducted For The First Time

Proteins associated with the regulation of organ size and shape have been found to respond to the mechanics of the microenvironment in ways that specifically affect the decision of adult cardiac stem cells to generate muscular or vascular cells.

Cell development for specific functions -- so-called cell differentiation -- is crucial for maintaining healthy tissue and organs. Two proteins in particular -- the Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1 or TAZ) -- have been linked with control of cell differentiation in the tissues of the lymphatic, circulatory, intestinal and neural systems, as well as regulating embryonic stem cell renewal.

An international collaboration of researchers has now identified that changes in the elasticity and nanotopography of the cellular environment of these proteins can affect how heart stem cells differentiate with implications for the onset of heart diseases.

Researchers at the International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS) collaborated with researchers in Finland, Italy, the Netherlands, Saudi Arabia and the Czech Republic in the study.

They engineered YAP and TAZ proteins that expressed green fluorescent protein so that their location within the cell could be tracked. They then prepared cell substrates from smart biomaterials displaying dynamic control of elasticity and nanostructure with temperature.

"Our data provide the first evidence for YAP/TAZ shuttling activity between the nucleus and the cytoplasm being promptly activated in response to dynamic modifications in substrate stiffness or nanostructure," explain the researchers.

Observations of gene expression highlighted the key role of YAP/TAZ proteins in cell differentiation. In further investigations on the effect of substrate stiffness they also found that cell differentiation was most efficient for substrates displaying stiffness similar to that found in the heart.

The authors suggest that understanding the effects of microenvironment nanostructure and mechanics on how these proteins affect cell differentiation could be used to aid processes that maintain a healthy heart.

They conclude, "These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design."

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Heart cells respond to stiff environments