fibroblast

Using a stem cell’s journey to teach kids science

/ Kevin McCormack / Leave a comment

THIS BLOG CAN ALSO BE HEARD AS AN AUDIOCAST ON SPOTIFY

As far as Aldo Pourchet is concerned you are never too young to learn about stem cells. Aldo should know. He’s a molecular and cellular biologist and the co-founder and CEO of Omios Bio, which develops immunotherapies for cancer, infectious and inflammatory diseases.

Aldo Pourchet

And now Aldo is the author of a children’s book about stem cells. The book is “Nano’s Journey! A Little Stem Cell Visits the Heart and Lungs.” It’s the story of Nano, a stem cell who doesn’t know what kind of cell she wants to be when she grows up, so she goes on a journey through the body, exploring all the different kinds of cell she could be.

It’s a really sweet book, beautifully illustrated, and written in a charming way to engage children between the ages of 5 and 8. I asked Aldo what made him want to write a book like this.

“I was interested in providing very general knowledge such as the principle of life, the basic logics of nature and at the same time to entertain. It was very important for it not to be a textbook.

“Why Stem cells? Because it is the most fascinating biology and they are at the origin of an organism and throughout its life play an essential role. They evolve and transform, so they have a story that unfolds. An analogy with children maybe. It’s easy to imagine children are like stem cells, trying to decide who they are, while adults are like differentiated cells because they have already decided.

“For the kids to appropriate the story, I thought that humanizing cells was important.  I wanted children to identify themselves with the cells and especially Nano, the little girl main character. It’s a book written for the children, in the first place. We tell the story at their level. Not try to bring them up to the level of life science.

Aldo says right from the start he had a clear idea of who he wanted the lead character to be.

“I think the world needs more female leaders, more female voices and influence in general and in every domain. So quite early it became natural for me that Nano would be a girl and also would have a strong character, curious and adventurous.

“Blasto came later because I was looking for a companion to share the adventure with Nano. Blasto is a fibroblast so he is not supposed to leave the Bone Marrow but fibroblasts are everywhere in our organism so I thought it was an acceptable stretch.

The drawings in the book are delightful, colorful and fun. Aldo says he had some ideas, rounded shapes for the cells for example and a simple design that reflected the fact that there are no lines in nature. Illustrator Jen Yoon took it from there:

“Based on Aldo’s direction and imagination, I envisioned the style like drawings on a chalkboard. Soft curves with rough textures. After that everything went smoothly. Following Nano’s journey with my iPad pencil, it felt like a boat ride at an amusement park.”

The books are written to be read aloud by parents, adults and teachers to kids. But, spoiler alert, we don’t find out what cell Nano decides to be in this book. She’s going to have more adventures in other books before she makes up her mind.

Regenerating damaged muscle after a heart attack

/ Kevin McCormack / Leave a comment

Cardio cells image

Images of clusters of heart muscle cells (in red and green) derived from human embryonic stem cells 40 days after transplantation. Courtesy UCLA

Every year more than 735,000 Americans have a heart attack. Many of those who survive often have lasting damage to their heart muscle and are at increased risk for future attacks and heart failure. Now CIRM-funded researchers at UCLA have identified a way that could help regenerate heart muscle after a heart attack, potentially not only saving lives but also increasing the quality of life.

The researchers used human embryonic stem cells to create a kind of cell, called a cardiac mesoderm cell, which has the ability to turn into cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells. All these types of cells play an important role in helping repair a damaged heart.

As those embryonic cells were in the process of changing into cardiac mesoderms, the team was able to identify two key markers on the cell surface. The markers, called CD13 and ROR2 – which makes them sound like extras in the latest Star Wars movie – pinpointed the cells that were likely to be the most efficient at changing into the kind of cells needed to repair damaged heart tissue.

The researchers then transplanted those cells into an animal model and found that not only did many of the cells survive but they also produced the cells needed to regenerate heart muscle and vessels.

Big step forward

The research was published in the journal Stem Cell Reports. Dr. Reza Ardehali, the senior author of the CIRM-funded study, says this is a big step forward in the use of embryonic stem cells to help treat heart attacks:

“In a major heart attack, a person loses an estimated 1 billion heart cells, which results in permanent scar tissue in the heart muscle. Our findings seek to unlock some of the mysteries of heart regeneration in order to move the possibility of cardiovascular cell therapies forward. We have now found a way to identify the right type of stem cells that create heart cells that successfully engraft when transplanted and generate muscle tissue in the heart, which means we’re one step closer to developing cell-based therapies for people living with heart disease.”

More good news

But wait, as they say in cheesy TV infomercials, there’s more. Ardehali and his team not only found the markers to help them identify the right kinds of cell to use in regenerating damaged heart muscle, they also found a way to track the transplanted cells so they could make sure they were going where they wanted them to, and doing what they needed them to.

In a study published in Stem Cells Translational Medicine,  Ardehali and his team used special particles that can be tracked using MRI. They used those particles to label the cardiac mesoderm cells. Once transplanted into the animal model the team was able to follow the cells for up to 40 days.

Ardehali says knowing how to identify the best cells to repair a damaged heart, and then being able to track them over a long period, gives us valuable tools to use as we work to develop better, more effective treatments for people who have had a heart attack.

CIRM is already funding a Phase 2 clinical trial, run by a company called Capricor, using stem cells to treat heart attack patients.

 

Molecular Trick Diminishes Appearance of Scars, Stanford Study Finds

/ cirmweb / Leave a comment

Every scar tells a story, but that story may soon be coming to a close, as new research from Stanford University reveals clues to why scars form—and offers clues on how scarring could become a thing of the past.

Reported last week in the journal Science, the research team pinpointed the type of skin cell responsible for scarring and, importantly, also identified a molecule that, when activated, can actually prevent the skin cells from forming a scar. As one of the study’s senior authors Michael Longaker explained in a press release, the biomedical burden of scarring is vast.

Scars, both internal and external, present a significant biomedical burden.

Scars, both internal and external, present a significant biomedical burden.

“About 80 million incisions a year in this country heal with a scar, and that’s just on the skin alone,” said Longaker, who also co-directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “Internal scarring is responsible for many medical conditions, including liver cirrhosis, pulmonary fibrosis, intestinal adhesions and even the damage left behind after a heart attack.”

Scars are normally formed when a type of skin cell called a fibroblast secretes a protein called collagen at the injury site. Collagen acts like a biological Band-Aid that supports and stabilizes the damaged skin.

In this study, which was funded in part by a grant from CIRM, Longaker, along with co-first authors Yuval Rinkevich and Graham Walmsley, as well as co-senior author and Institute Director Irving Weissman, focused their efforts on a type of fibroblast that appeared to play a role in the earliest stages of wound healing.

This type of fibroblast stands out because it secretes a particular protein called engrailed, which initial experiments revealed was responsible for laying down layers of collagen during healing. In laboratory experiments in mouse embryos, the researchers labeled these so-called ‘engrailed-positive fibroblast cells,’ or EPF cells, with a green fluorescent dye. This helped the team track how the cells behaved as the mouse embryo developed.

Interestingly, these cells were also engineered to self-destruct—activated with the application of diphtheria toxin—so the team could monitor what would happen in the absence of EPF cells entirely.

Their results revealed strong evidence that EPF cells were critical for scar formation. The scarring process was so tied to these EPF cells that when the team administered the toxin to shut them down, scarring reduced significantly.

Six days later the team found continued differences between mice with deactivated EPF cells, and a group of controls. Indeed, the experimental group had repaired skin that more closely resembled uninjured skin, rather than the distinctive scarring pattern that normally occurs.

Further examination of EPF cells’ precise function revealed a protein called CD26 and that blocking EPF’s production of CD26 had the same effect as shutting off EPF cells entirely. Wounds treated with a CD26 inhibitor had scars that covered only 5% of the original injury site, as opposed to 30%.

Pharmaceutical companies Merck and Novartis have already manufactured two types of CD26 inhibitor, originally developed to treat Type II diabetes, which could be modified to block CD26 production during wound healing—a prospect that the research team is examining more closely.