Stem cell stories that caught our eye: spina bifida, review of heart clinical trials, tracking cells and cell switches

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cells boost fetal surgery for spina bifida. Fetal surgery to correct the spinal defect that causes spina bifida has revolutionized treatment for the debilitating birth defect in the past few years. But for one of the researchers who pioneered the surgery it was only a half fulfilled hope. While the surgery let most of the treated kids grow up without cognitive deficits it did not improve their ability to walk.

spina_bifida-webNow that researcher, Diana Farmer at the University of California, Davis, has found a way to complete the job. Though it has only been used in an animal model so far, she found that when you engineer a stem cell patch that you insert into the gap before you push the protruding spinal cord back in its place during surgery, the animals are able to walk within a few hours of birth.

Specifically, she used a type of stem cell found in the placenta that has been shown to protect nerves. She incased those cells in a gel and placed them on a scaffold to hold them in place after transplant. All six lambs that had surgery plus the cell transplant walked. None of the ones who just had surgery did.

“Fetal surgery provided hope that most children with spina bifida would be able to live without (brain) shunts,” Farmer said. “Now, we need to complete that process and find out if they can also live without wheelchairs.”

CIRM awarded Farmer’s team funds in March to carry this work forward and prepare it for a possible clinical trial. The animal study appeared in Stem Cells Translational Medicine this week and the university’s press release was picked up by HealthCanal.

Thorough, digestible review of heart trials. Kerry Grens, writing in The Scientist, has produced the most complete and understandable review of the clinical trials using stem cells to treat heart disease that I have read. More important she provides significant detail about the three large Phase 3 trials that are ongoing that could provide make-or-break outcomes for using bone marrow stem cells for patients developing heart failure.

The bulk of the piece focuses on research using various types of mesenchymal stem cells found in bone marrow. All three of the late stage clinical trials use those cells, two use cells from the patient’s own marrow and one uses cells from donors. Grens uses a broad spectrum of the research community describe what we currently know about how those cells may work and more importantly, what we don’t know. The experts provide a good point-counter-point on why there are so many clinical trials when we don’t really know those stem cells’ “method of action,” why they might make someone’s heart stronger.

However she leads and ends with work CIRM funds at Cedars-Sinai and Capricor Therapeutics in Los Angeles. That work uses cells derived from the heart called cardiosphere-derived cells. Early trials suggested these cells might be better at reducing scar tissue and triggering regrowth of heart muscle. Those cells are currently being tested in a Phase 2 study to try to get a better handle on exactly what their benefit might be.

Monitoring stem cells after transplants. Early attempts to use stem cells as therapies have been hampered by an inability to see where the cells go after transplant and if they stay the desired location and function. A team at Stanford has used some ingenious new technologies to get over this hurdle, at least in laboratory animals.

Using a homegrown technology that recently won a major innovation prize for a Stanford colleague, optogenetics, the team was able to selectively activate the transplanted cells. Then they used the older technology, functional Magnetic Resonance Imaging (fMRI), to see if the cells were working. Because cell transplants in the brain have led to some of the most difficult to interpret results in humans, they chose to work with nerve stem cells transplanted into the brains of rats. The work was partially funded by CIRM.

Starting with iPS type stem cells made from Parkinson’s patients’ skin, they inserted a gene for a protein that is sensitive to certain wavelengths of light. They then matured those cells into nerve stem cells and implanted them along with a tube that could transmit the right wavelength of light. Over the course of many months they measured the activity of the cells via fMRI with and without the light stimulation. Because the fMRI measures blood flow it by default detects active nerve cells that require more nutrients from blood than inactive cells. Senior researcher, Jin Hyung Lee described the value of this imaging in the university’s press release picked up by HealthCanal:

“If we can watch the new cells’ behaviors for weeks and months after we’ve transplanted them, we can learn — much more quickly and in a guided way rather than a trial-and-error fashion — what kind of cells to put in, exactly where to put them, and how.”

Understanding cell’s switchboard may speed therapy. Cells function by switching genes on and off. Learning which switches to hit to maximize stem cells’ ability to multiply and mature into desired cell types has occupied a significant part of the stem cell research community for years. Now, a team at the Salk Institute has shown that two known genetic switches pack an additive punch when working together.

Both those signaling processes, one called Wnt and one called Activin, are needed for stem cells to mature into specific adult tissue. The Salk team led by Kathy Jones found that when working together the two signals activate some 200 genes. Wnt seems to load the cellular equipment needed for copying the cells and Activin increases the speed and efficiency of the process. In an institute press release picked up by Science Newsline, Jones discussed the practical implications of the finding:

“Now we understand stem cell differentiation at a much finer level by seeing how these cellular signals transmit their effects in the cells. Understanding these details is important for developing more robust stem cell protocols and optimizing the efficiency of stem cell therapies.”

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