Scar-forming cells in the heart converted directly into beating heart muscle

Last year, our grantees at Gladstone Institutes worked a neat trick: they converted the scar-forming cells of the heart directly into beating heart cells in living mice. (We wrote about that work here.)

The cells they converted, also called fibroblasts, are the ones that create scar tissue in the heart after a heart attack. Their work created the possibility of directly replacing scar tissue with healthy heart muscle following a heart attack.

But that work was in mice. The real test was to work the same conversion in human tissue, which they just published in the journal Stem Cell Reports. The group, which includes senior author Deepak Srivastava and Benoit Bruneau, coerced human fibroblasts in the lab dish to convert directly to beating heart tissue.

A press release from the Gladstone Institutes quotes Srivastava:

“With more than five million heart attack survivors in the United States and climbing each year, our findings come at a critical time. We’ve now laid a solid foundation for developing a way to reverse the damage—something previously thought impossible—and changing the way that doctors may treat heart attacks in the future.”

The group did run into hurdles along the way. They’d originally used a group of three factors to convert the mice fibroblasts to heart muscle. Those same three factors weren’t effective in human cells. Instead, they had to start over, testing a large pool of different factors before narrowing down the group of factors needed to work the conversion. They still have some work to do, too. Only about 20% of the cells converted. Gladstone quotes the lead author Ji-dong Fu talking about this effect:

“Clearly, there are some yet-to-be-determined barriers preventing a more complete transformation for many of the cells. For example, success rates might be improved by transforming the fibroblasts within living hearts rather than in a dish—something we also observed during our initial experiments in mice.”

Gladstone produced this cool 3-D animation about the work:

3D reconstruction of a cardiomyocyte (heart muscle cell), derived from a fibroblast via direct reprogramming. Direct reprogramming allows scientists to transform one cell type into another without first reverting back to the pluripotent, stem-cell state. [Animation: Scott Metzler]

CIRM funding: Deepak Srivastava (RB3-05174); Benoit Bruneau (RN2-00903); Paul Delgado-Olguin (TG2-01160)

Amy Adams

Through their lens: Alexander Seutin learns how computer technology can help unlock secrets of blood cancers

This summer we’re sponsoring high school interns in stem cell labs throughout California. We asked those students to contribute to our Instagram photos and YouTube videos about life in the lab, and write about their experiences.

Alexander Seutin did a stem cell research internship this summer in the laboratory of Ravi Majeti at Stanford University.

This summer I worked at the Stanford school of medicine, conducting research in a lab run by principal investigator, Ravi Majeti in the stem cell department. We focus on a group of hematopoietic clonal disorders called myeloproliferative neoplasms. These blood disorders are characterized by their unregulated trilineage proliferation in myeloid cells, resulting in irregular hematopoiesis, often leading to many other complications down the line.

This category of diseases was first discovered in 1951 by William Dameshek who called attention to the morphologic similarities between chronic myeloid leukemia, polycythemia vera, essential thrombocythemia and primary myelofibrosis. In the years to follow, stem cells would emerge at the forefront of science and people would realize that these diseases produce cells that share a similar hierarchy to the healthy hematopoietic stem cell. It was then that people began to think about a leukemia or cancer stem cell.

In my project I analyzed gene expression data from microarrays run on these types of stem cells taken from individuals who have obtained one of these disorders. I then had to figure out how to interpret this immense quantity of data that had been given to me and it was then that I began to gain a real appreciation for what we are doing. I learned how to use many bioinformatics tools such as DAVID, gene expression commons, gene set enrichment analysis, hierarchical clustering, and many others all while gaining a deeper insight as to what I was actually doing. This insight not only allowed me to utilize these skills within my own project but also permitted me to gain a more universal understanding of modern science.

I slowly began to become more comfortable with my field through reading scientific papers, attending lab meetings, and by doing research on my own. This then allowed me to absorb more and more information about what people are presently doing which would not only show me how amazing the things we are doing are but more importantly teaching me that there is a giant window of opportunity in research, opened by modern technology, computer programming and the whole of bioinformatics. It is one that my generation will have to learn to exploit, hopefully allowing us to discover something great.

Alexander Seutin

Through their lens: Anne McDermott works on better ways of culturing embryonic stem cells

This summer we’re sponsoring high school interns in stem cell labs throughout California. We asked those students to contribute to our Instagram photos and YouTube videos about life in the lab, and write about their experiences.

Anne McDermott did a stem cell research internship this summer in the laboratory of Jan Nolta at the University of California, Davis.

My name is Anna McDermott, and at the beginning of this summer I was offered the opportunity of a lifetime. Chosen as one of ten creativity students for the UC Davis Institute for Regenerative Cures, I spent my summer working at the Institute for Regenerative Medicine at the UC Davis Medical Center. During these eight weeks I have learned about cell culture, attended a class on stem cells, and gained invaluable experience in the lab.

My focus during this internship was my project, in which I compared various feeder free substrates for possible future ways of culturing human embryonic stem cells. I cultured human embryonic stem cells on four different feeder-free substrates. Embryonic stem cells offer great potential to regenerative medicine. Because of their pluripotency, or ability to differentiate in any cell type in the body, they offer enormous potential to medicine. Embryonic stem cells may one day be able to treat spinal cord injuries, or improve eyesight in patients with macular degeneration. However, before embryonic stem cells can be used to save and improve life, several difficulties must be overcome.

One of the challenges facing the use of embryonic stem cells is the risk of contamination and the variation that results from using animal component containing mediums. Embryonic stem cells are typically grown on live animal cells, mouse embryonic fibroblasts, and are fed with serum containing media. By using feeder-free substrates and xeno-free mediums the risk of contamination with animal virus or prion material can be eliminated. Variability in results from lab to lab will be reduced, and greater expansion of cell lines will be possible.

Although I had researched stem cells while creating my website focused on the current and potential therapies stem cell promise, working in the lab with researchers changed my perspective about stem cell research. Reading information through research provided me with information. However, observing, and working with stem cells provided me with a greater understanding about the science behind stem cells.

During my time at the lab I also witnesses the research being conducted in the lab for various stem cell therapies, from Huntingtons disease to ALS to wound repair. The dedication and passion of these scientists was inspiring. From a young age my father, an opthamologist, instilled an interest in science and medicine. Although I was at first unsure which path I should take to pursue both my passion for both medicine and research, this internship has shown me that through stem cell research I can work to research and develop treatments and cures for diseases, diseases that were before untreatable or incurable. This summer has been an unforgettable and life changing experience.

I would like to thank Whitney Cary, for teaching and inspiring me, Jan Nolta, Nolta lab, Gerhard Bauer, CIRM, and the UC Davis Stem Cell Program. Thanks for an amazing summer!

Anne McDermott