Stem Cell Stories that Caught Our Eye: perfecting pluripotency, building a spinal cord, and CIRM Board funds new clinical trials

Here are the stem cell stories that caught our eye this week. 

Perfecting Pluripotency in stem cells.

The power of pluripotent stem cells lies in their ability to become any cell type in the body. But how did they get this impressive power?

Scientists from the University of Zurich in Switzerland think they might have an answer. In a study published in Nature Cell Biology, the team discovered that stem cells in the early stage embryo express a protein called Pramel7. This protein is like an eraser. Its presence ensures that a cell’s DNA is free of epigenetic marks, which are chemical tags that tell genes to switch on or off.

Embryonic stem cells have a blank slate meaning their genomes are free of epigenetic marks. This allows them to follow any developmental path and become any cell in the body. But as embryonic stem cells develop into more specialized adult cells, epigenetic marks called methyl groups are added to their genomes to effectively seal off genetic material containing genes that aren’t necessary to the fate of that cell.

The team found that Pramel7 was active in the stem cells of embryos that were only a few days old. Interestingly, when they studied embryonic stem cells grown in a petri dish outside of embryos, these stem cells didn’t express Pramel7 and consequently had more methyl marks on their DNA. These findings, which were captured in coverage by Phys.org, led the scientists to dub Pramel7 expressing embryonic stem cells as the “perfect allrounders.”

“Despite its short action period of just a few days, Pramel7 seems to play a vital role: When the researchers headed up by Cinelli and Santoro switched off the gene for this protein using genetic tricks, development remained stuck in the embryonic cell cluster stage. In the cultivated stem cells, on the other hand, Pramel7 is rarely found. This circumstance could also explain why the genetic material of these cells contains more methyl groups than that of natural embryonic cells.”

Just a few days old embryonic cell clusters: with functional Pramel7 (left), without the protein (right) – the development of the stem cells remains stuck and the embyos die. Credit: Paolo Cinelli, USZ

In future studies, the scientists will use their newly found knowledge about stem cell pluripotency to study how stem cells can regenerate bone fractures in patients. Before they can replace broken and damaged bones, they argue that “we have to know how stem cells work [first].”

CIRM Invests in Treatments for Stroke, Cancer and Blood Disorders.

Yesterday, the CIRM governing Board convened for our June ICOC meeting to consider the funding of stem cell research applications ranging from early, discovery stage studies to clinical trials.

Two new trials were added to our pipeline. SanBio was awarded $20 million to test a mesenchymal stem cell-based treatment for patients that have suffered from a stroke. UCSF received $12.1 million for a hematopoietic stem cell treatment for babies with a blood disorder called alpha thalassemia major. The stem cells are taken from the mother’s bone marrow and transplanted into the womb before the baby is born in hopes of improving the chances of a healthy birth.

The Board also approved 13 early stage research projects that are part of our Discovery Quest Awards Program, which promotes the discovery of promising new stem cell-based technologies that could be translated to enable broad use and ultimately improve patient care. You can read more about these studies in yesterday’s news release.

The Board meeting was particularly memorable one. A patient named Caleb Sizemore, who participated in the CIRM-funded Capricor trial for Duchenne muscular dystrophy, spoke to the Board about his experience in the trial and the importance of funding stem cell research for patients.

We also said an emotional goodbye to two important members of the CIRM team, President Randy Mills and General Counsel James Harrison. Randy will be the new President and CEO of the National Marrow Donor Program and James will be returning to his role as a partner at the law firm of Remcho, Johansen & Purcell, LLP.

We’ll be blogging more about the events of our Board meeting next week, so stay tuned!

CIRM President and CEO Dr. Randy Mills receives an award of appreciation and a CIRM plaque with his family.

Building a spinal cord comes down to location, location, location. (Todd Dubnicoff)

The spinal cord is an amazing part of our anatomy. Its long bundle of nerve cells acts like an elaborate highway starting from the brain, running down the spine and jutting out to countless “off-ramps” that make connections to our limbs and organs. These nerve cells are critical for bringing in sensory information from the body up to the brain and for sending out movement instructions from the brain down to our muscles. Assuming these cells aren’t equipped with their own GPS technology, how do they determine their precise location and turn into the right type of cell while building this information highway during embryo development?

A normal developing spinal cord (left) showing precise patterns of gene activity (red, blue, green demarcating different types of cells). In a spinal cord in which one of the signals is disrupted (right) the accuracy of gene activity has been lost. Image: Anna Kicheva

 

This week, a collaborative team of European scientists answered a large piece of that fundamental question. Reporting in Science, the researchers show evidence that progenitor, or early stage, nerve cells in developing mouse embryos sense the concentration of two proteins that spread out in opposite directions along the dorsal/ventral axis (from the belly to the back) of the body. Each progenitor nerve cell encounters a specific local concentration of these opposing protein gradients and then activates an appropriate set of genes in response.

Through some in-depth number crunching, the team showed that either gradient alone was not as precise in providing dorsal/ventral position information to cells compared to when both gradients are in place. They also showed that these gradients remained intact for the first 30 hours of development and then dissipated which indicates their importance in the earliest moments of life.

Anna Kicheva, the team lead for the research group the Institute of Science and Technology in Austria, explained the significance of these findings in a press release:

“We’ve made an important step in understanding how the diverse cell types in the spinal cord of a developing embryo are organized in a precise spatial pattern. The quantitative measurements and new experimental techniques we used, as well as the combined effort of biologists, physicists and engineers were key. This allowed us to gain new insight into the exquisite accuracy of embryonic development and revealed that cells have remarkable ability of to orchestrate precise tissue development.”

These new insights will not only provide a better understanding of how spinal cord development works but could also create new therapeutic approaches to diseases and injuries. James Briscoe, the senior author from the Francis Crick Institute in the United Kingdom, thinks these finding could also shed light on the development of other parts of the body:

“It’s likely that similar strategies are used in other developing tissues and our findings might be relevant to these cases. In the long run this will help inform the use of stem cells in approaches such as tissue engineering and regenerative medicine.”

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