Hed: Stem cell stories that caught our eye: the why’s of heart failure, harnessing stem cells’ repair kits and growing 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.

Stem cell model sheds light on heat failure. Pretty much everyone who has heart failure due to cardiomyopathy—where the heart muscle doesn’t work as effectively as it should—or has a condition that could lead there, is taking a beta blocker. The beta-andrenergic pathway, a key molecular pathway in the heart, dysfunctions in patients with cardiomyopathy and we have never known exactly why. We just know these drugs help.

Now, a team at Stanford led by Joseph Wu has used skin samples from patients and normal subjects to create reprogrammed iPS type stem cells, grown them into heart muscle, and compared them at a very fine-tuned molecular level.

Some patients have a mutation in a protein called TNNT2 in heart muscle fibers, which regulates muscle contraction. So, one thing they looked at was the impact of that mutation. Wu’s team followed the actions triggered by this mutation and found they lead to the beta-andrenergic pathway. Wu explained the value he sees in this fundamental understanding of the disease in a Stanford press release:

“As a cardiologist, I feel this basic research study is very clinically relevant. The beta-andrenergic pathway is a major pharmaceutical target for many cardiac conditions. This study confirms that iPS-cell-derived cardiomyocytes can help us understand biologically important pathways at a molecular level, which can aid in drug screening.”

CIRM did not fund this project but we do fund other projects in Wu’s lab including one to advance the use of iPS cells as models of heart disease, one using tissue engineering to repair damaged areas of the heart and one using embryonic stem cells to generate new heart muscle.

Harnessing stem cells’ repair kits. Stem cells repair tissue in multiple ways, but primarily by maturing into cells that replace damaged ones or by excreting various chemicals that give marching orders to neighboring cells to get busy and make the repairs. Those chemicals, collectively called paracrine factors, get excreted by the stem cells in vessels known as exosomes. So, a team at Temple University in Philadelphia decided to try injecting just the exosomes, rather than whole stem cells to repair heart damage. It seemed to work pretty well in mice.

Stem cells release exosomes, tiny vessels that act as repair kits.

Stem cells release exosomes, tiny vessels that act as repair kits.


After treatment with the exosomes, mice with induced heart attacks showed fewer heart cells dying, less scar tissue, more development of new blood vessels and a stronger heart function. The head of the Temple team, Raj Kishore, described the result in a university press release distributed by EuekaAlert:

“You can robustly increase the heart’s ability to repair itself without using the stem cells themselves. Our work shows a unique way to regenerate the heart using secreted vesicles from embryonic stem cells.”

The team went on to isolate a specific regulatory chemical that was among the most abundant in the exosomes. That compound, a type of RNA, produced much of the same results when administered by itself to the mice—intriguing results for further study.

Good primer on using stem cells to grow organs. The Wisconsin State Journal ran a nice primer in both video and prose about what would theoretically go into building a replacement organ from stem cells and some of the basic stem cell principals involved. The piece is part of a series the paper produces with the Morgridge Institute at the University of Wisconsin. This one features an interview with Michael Treiman of Epic Systems:

“The biggest challenge right now is that we can push a stem cell to be a particular type of cell, but in a tissue there’s multiple cells. And an organ like your heart or brain isn’t just made of one cell type; it’s made of many cell types working together.”

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