Stem cell stories that caught our eye: reversing aging, mature hearts, arthritic knees and tiny organs

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.

Young brain cells (top) show little of the molecule that impairs stem cell function (green) that is abundant in old cells (bottom).

Young brain cells (top) show little of the molecule that impairs stem cell function (green) that is abundant in old cells (bottom).

Making stem cells feels young again. Stem cells are supposed to rejuvenate our tissues, whether brain or muscle, and keep them functioning at their peak. But the aging process seems to poison the environment where stem cells reside and prevent them from getting the job done.

A CIRM-funded team at the University of California, Berkeley, has found a drug that can reverse the effect of aging and make the stem cells function better and in turn make tissues behave like younger versions of brain or muscle. Their previous work had shown that old tissues had much more of one growth factor, TGF-beta1, than young tissue. When the team, led by David Schaffer and Irina Conboy, blocked the activity of that growth factor with a cancer drug already in clinical trials they saw rejuvenated youthful tissue—in mice.

HealthCanal picked up the university’s press release, in which Schaffer described the broad effect of the treatment:

“We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle. That is good news, because if every tissue had a different molecular mechanism for aging, we wouldn’t be able to have a single intervention that rescues the function of multiple tissues.”

The team, however, noted that multiple molecular signals are in play in the aging stem cell’s environment and optimum intervention may require using more than one drug and getting the dosages just right. Conboy said that the task was to “recalibrate the environment to be youth-like.”

Maturing of the heart. Scientists can turn embryonic stem cells into most forms of adult tissue, but often those tissues don’t function like fully mature forms of the organ they are supposed to be. Now a consortium of researchers has identified a molecular switch that seems to be able to take stem cells and get them to form fully mature heart muscle.

In an interview with Genetic Engineering & Biotechnology News, senior author on the paper Hannele Ruohola-Baker of the University of Washington noted the breakthrough:

“Although we can now induce embryonic stem cells to become heart cells, getting them to mature to an adult-like state remains a significant challenge. We believe we’ve now found the master switch that drives the maturation process.”

The researchers found the molecular switch by studying many of the genetic switches called micro-RNAs in both young and old heart muscle cells. The one linked to helping stem cells mature interestingly is also involved in up-regulating metabolism and it makes sense that a supercharged metabolism would be valuable for fully functional heart muscle.

Some answers may be coming on stem cells and knees. While many clinics around the word offer to treat arthritic knees with stem cells taken from a patient’s own fat—often for large sums of money—very little data exist on the outcomes of those treatments. So, it was great to read this week that a European consortium is about to launch a large trial that should provide some quality data.

The ADIPOA-2 trial will enroll 150 patients in a randomized way so that the stem cell treatment can be compared to standard therapies, and the researchers will handle processing of the fat stem cells in a consistent way across clinics in four countries. It follows a phase 1 ADIPOA trial with 18 patients that showed promising results.

Frank Barry of the National University of Ireland Galway is coordinating the phase 2 trial and was quoted in the university’s press release picked up by HealthCanal:

“The results from ADIPOA’s first-in-man-trials were very encouraging and paved the way for another study to further test the safety and effectiveness on a wider scale. ADIPOA-2 is bringing together Europe’s leading scientific, clinical and technical expertise on this project.”

A lingering question remains about how long any benefit from the stem cell therapy will last. Some researchers have suggested that fat stem cells can only form soft cartilage like in your ear lobe and not the articular hard cartilage normally in your knee. So, it will take some years of follow-up to see if any new cartilage made by the stem cells can stand up to the beating of a good tennis match or hike up a mountain.

CIRM funds a research team at the University of Calirfornia, San Diego, that believe they have found a way to get embryonic stem cells, which are more versatile than fat stem cells, to form the hard articular cartilage.

Great hope in tiny little organs. For the past couple years one of the hottest areas of stem cell science has been growing stem cells in 3-D cultures in the lab and getting them to self organize into multi-tissue layers that mimic some function of one of our vital organs. It has been done for the eye, lung, liver, kidney and brain, but the first was the intestine, and the researcher behind the advance, Hans Clevers, dubbed them “organoids.”

The journal Nature just published a good Q&A interview with Clevers who works at the Hubrecht Institute Utrecht, the Netherlands. In it he describes how organoids will be a useful tool for drug screening and how his team is working on ways that organoids made from a patient’s own cells could be tested in the lab for sensitivity to specific cancer therapies.

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