Stem cell stories that caught our eye: colon cancer relapse and using age, electricity and a “mattress” to grow better hearts

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 yield markers for relapse in colon cancer. Some colon cancer patients do fine after surgery without any chemotherapy, but it has been hard to predict which ones. A CIRM-funded team at the University of California, San Diego, with collaborators at Stanford and Columbia Universities, found a predictor for the need for chemotherapy by looking at the patients’ cancer stem cells.

colon cancer stem cells

Patients whose colon cancer stem cells tested positive for CDX2 (brown) had a better prognosis.

Previously researchers have looked for markers in the tumors themselves for differences between those who require chemotherapy and those who don’t. Those efforts generally come up empty handed. The current team instead looked for differences in the patient’s cancer stem cells. They found that patients whose stem cells lacked one protein marker called CDX2 did poorer with surgery alone and were candidates for follow-up chemotherapy.

The team published its work in this week’s New England Journal of Medicine and it got wide pickup by online news outlets, but that coverage varied somewhat depending on which group the reporters called. Medical News Today provides the Columbia angle. Newswise distributed a press release with the San Diego voice and BlackDoctor.org used quotes from Stanford as well as the American Cancer Society. The latter lets Stanford’s Michael Clark remind readers that this was a retrospective look back at prior cancer patients and the conclusions need confirmatory studies.

 “The data is extremely strong, but you need a prospective analysis to be 100 percent sure. It should be validated in a prospective trial.”

 

Three studies aim for better heart cells. While researchers have been turning stem cells into heart muscle in lab dishes for several years, getting them to function like normal heart cells either in the dish or when transplanted into animals has been tough. Three research groups published studies this week showing different approaches to making better heart muscle.

normal heart cells

Normal heart muscle cells, courtesy Kyoto University

Age matters

 Biologists at Japan’s Kyoto University found a sweet spot in the age of new muscle cells when they were most likely to engraft and survive when transplanted in animals. They first created reprogrammed iPS-type stem cells and then matured them toward becoming heart muscle for four, eight, 20 and 30 days. The 20-day cells proved the most able to engraft in the mouse hearts and improve their function as seen by echocardiography.

The Kyoto team published its results in Scientific Reports and BiotechDaily wrote an article on the work.

Give them a jolt. 

A group of physician engineers at Columbia University found that exposing lab grown heart muscle cells to electrical stimulation that mimicked the signals the cells would receive in a fetus resulted in stronger, more synchronized heart muscle. They started by engineering the heart muscle cells to grow in three dimensions and then added the electrical signals.

 “We applied electrical stimulation to mature these cells, regulate their contractile function, and improve their ability to connect with each other. In fact, we trained the cell to adopt the beating pattern of the heart, improved the organization of important cardiac proteins, and helped the cells to become more adult-like,” said Gordana Vunjak-Novakovic, the lead author on the paper published in Nature Communications.

 NewsMedical picked up the university’s press release.

Give them a mattress. 

 A team at Vanderbilt University in Tennessee found that growing the heart muscle cells on a commonly used lab gel called Matrigel resulted in cells with a shape and contractile function that matched normal heart tissue. The Matrigel formed a cushiony substrate that one team member referred to as a “mattress” for the cells to grow on that is more like the living environment in an animal than the usual lab dish.

ScienceDaily ran the university’s press release about the study published in Circulation Research. In the release, the team speculated that the matrigel worked through a combination of the flexibility of the gel and unknown growth factors released by the gel itself.

With heart disease still a leading cause of death, learning how to make better repair tissue could lead to major improvements in quality and length of lives. Of the 600-plus stem cell clinical trails currently active around the world, at least 70 target heart disease, but very few are striving to provide new tissue to repair damaged heart muscle. Generally, they are using stem cells that secrete various factors that help the heart heal itself. CIRM funds one of those trials being conducted by Capricor.

What…exactly…do you do? How 12 year olds helped me learn how to talk about science

Jackie Ward in her lab at UC San Diego

Jackie Ward in her lab at UC San Diego

Jackie Ward is a graduate student at the University of California, San Diego (UCSD), and received a training grant from CIRM while studying for her PhD. At UCSD Jackie uses stem cells as a model to study rare neurodegenerative diseases in the lab of Albert La Spada. Her work as a PhD student focuses on a rare form of inherited neurodegeneration called spinocerebellar ataxia. From time to time Jackie shares her experiences with us. Here’s her latest.

One of the many questions I get over my annual trek home during the holidays is “What…exactly…do you do?” This is usually couched somewhere between “have you learned to surf yet?” and “how’s the weather?” In the past, I preferred to talk about my surfing skills (very minimal) and the sunshine (always amazing, thanks San Diego), more than what I do every day. It’s amazing how this seemingly innocuous question can be the most difficult to answer. Because we’re used to presenting our work in lecture formats or lengthy scientific papers, summing it up in three sentences of non-jargon can be difficult. A similar thought was outlined recently at UCSD, by the actor and science advocate Alan Alda. The title of his presentation, “Getting the Public Past a Blind Date with Science,” highlighted the uncomfortable feelings many people have towards science. Like any relationship, sustained communication and trust is necessary for success. Unfortunately, on many scientific issues, that relationship has suffered. As a PhD student, I am constantly surrounded by my peers—other scientists who know exactly what I mean when I use terms like “reprogramming” or “retinal photoreceptor.” While these scientist-to-scientist conversations are vital to our work, we often forget that it is equally, or perhaps more, important to have conversations with people who have no idea what we do. As any CIRM- or NIH-funded lab is well aware, a significant portion of our funding comes from taxpayer dollars. It’s these “investors” to whom we ultimately report back. This conversation is challenging. Not only do we have to change our language, we have to remember what it was like to not know everything we do now. The best practice I’ve gotten in this regard is talking to kids. Seventh graders seem to be less afraid to ask you questions or call you out on something that doesn’t make sense to them. (Now that I think about it, it might be beneficial to include some 13-year-olds on our grant review panels.) My graduate program allows students to fulfill their teaching requirement by doing science outreach activities. I chose to do this with the Salk Institute’s mobile science lab, where real scientists are connected to local middle schools to discuss their jobs and lead hands-on science labs. I didn’t realize how valuable this experience was until it started to become easier for me to answer the “what do you do” question. I changed the words I use. I replaced the word “reprogram” with “rewind” and “retinal photoreceptor” with “eye cell.” Unexpectedly, I think this practice helped me become a better communicator when I talk to other scientists now too. I try not to assume a certain level of knowledge with anybody. While I still love talking about pretending to surf and gloating about the weather, I’ve become more fond of the “what do you do” question. I hope to only improve with time. It’ll be my small contribution for getting science to that second date.