Stem Cells in Injured Mice Give Them Huge Muscles for Life

Stem cells injected in injured legs helped them grow back almost twice their normal size and stay that way for years.

A happy accident may hold the key to healing muscle diseases and granting humans incredible physiques. Researchers at the University of Colorado at Boulder and the University of Washington discovered that stem cells injected into mouse muscles led to increased growth for the rest of the mouse’s life. Young mice with injured legs were given donor muscle stem cells from other young mice. Those injuries not only healed, but muscle mass increased 50% and muscle volume increased by an incredible 170%! Performance tests show the muscles were twice as strong as normal, and still above average when you control for size. Two years later, about the lifetime of a mouse, the legs were still bigger and stronger than normal, much to the scientists surprise. The study was recently reported in the journal Science Translational Medicine. I had a chance to speak with Bradley Olwin at UC Boulder to discuss his work and the possible applications in the future. He thinks that the muscle growth effect, if it could be reproduced in humans, may be a means to treat degenerative illnesses like Muscular Dystrophy. I think that this is another step towards super powered humans.

Olwin’s team (including graduate student John K. Hall) was exploring the best way for transplanting muscle satellite cells and trying to figure out how long these cells would survive in their new hosts. Some growth and recovery after injecting stem cells wouldn’t have been unheard of, but it wasn’t the focus of the study. Olwin was caught unawares by the scale of muscle growth and how long it lasted. For some reason, the stem cells weren’t simply multiplying and replacing old damaged cells. They formed new connections to myofibers (standard muscle cells) and their numbers in the muscle increased significantly. In other words, whatever the transplanted stem cells were doing, it was far beyond simply repairing damage and returning things to normal. Happily, the research team found no evidence of increased tumors in the mice. Despite all the amazing growth, cancer didn’t seem to be a problem.

(B) Strength for stem cell treated muscle (green) was nearly double that of normal tissue. (C) When accounting for differences in size, the treated muscles were still stronger than normal.

It’s really exciting to see temporary muscle growth turned into life long muscle retention. The implications for humans are astounding. The MDA provided some of the funding for this research, and it’s possible that this discovery could help us treat illnesses like Muscular Dystrophy as well as combat muscle loss associated with aging. In the long term, I think applications could extend far beyond that. Imagine injections that you would receive in your twenties that would let your muscles stay big and strong without the need for much exercise – and you could keep those muscles for the rest of your life! Yes, people with muscular diseases would want those treatments, but so would everyone else.

Of course, we shouldn’t get too far ahead of ourselves here. This research has plenty of issues that may keep it from granting humans super-physiques, and Olwin had some fundamental critiques of using stem cell transplants to heal muscles that we’ll get to later. First, I should mention that only injured legs in mice were granted increased muscle growth. When stem cells were injected into healthy mouse muscle nothing really happened. There’s something about the injury that stimulates the transplant. That injury, also, was inflicted in a directed way (with barium chloride injections). It’s unclear whether a natural injury, or muscle loss due to disease, would stimulate stem cells to act in a similar way. However, in studies with dystrophic mice (who are genetically induced to have MD) healthy well-connected muscle tissue did develop after stem cell transplant (that work has yet to be published).

All the mice in the study were also fairly young when treated (three months) and the donors for the stem cells were the same age. Transplanting stem cells from young mice to young mice means we don’t know if age at the time of injury/treatment plays a major role in the effects. What if you could only get the stem cell treatments when you were 15? Most people on Earth would be disqualified.

The transplantation process itself is still being optimized. Olwin and colleagues found that you really had to get the donor cells when they were still attached to muscle fibers. Stripping them down and culturing them (as is done with many stem cell treatments) seems to decrease effectiveness. Remarkably, only about 10 to 50 stem cells were used for each mouse. That’s a surprisingly small number of cells. Olwin says that Hall and Chamberlain are already working on performing similar transplants in dogs. Clinical work in humans could be feasible in a few years.

However, Olwin pointed out a big drawback in using stem cell transplants to treat muscles. Every muscle would need its own injection. Furthermore, it’s unclear how well these cells would migrate in larger muscles (the ones in mice are very small, remember). You might have to gather hundreds (thousands?) of donor cell sets (each a group of 10 to 50 cells that are connected to muscle fibers) and then inject them into each muscle. Effectively you would have hundreds of microtransplants to perform and work with. Olwin says that small muscles and limited transplant regimes (say for the fingers of a hand) might be possible in the fairly near term. Larger scale ideas may not be feasible for a very long time (if ever).

Luckily, Olwin is already moving forward with a different approach. He’s always been more of a biochemist, and his idea is to mimic the donor stem cells’ effects using the right chemicals. Instead of stem cell transplants, we could use drugs that recreate the life long muscle mass increase. Olwin’s already tracking down the right signaling pathways, and has even had some success with dystrophic mice (that work is not yet published). Chemical signals seem better than stem cells for this application. By fooling muscles into taking the actions they would have taken had they received a transplant, Olwin is creating a possible systematic approach to treating muscle loss. You don’t need hundreds of micro-transplants, you just need one substance (or drug cocktail) that could be injected anywhere in the skeletal-muscular system. We’ve seen similar approaches proposed with myostatin, the hormone that tells muscles to stop growing. It seems possible that the future of muscle growth lies in pills or injections that trick the body into pumping itself up.

That sounds just fine by me. I love exercise, but I wouldn’t mind cheating on my workout now and then if it was safe and effective.

[image credits: Bradley Olwin]
[sources: Hall et al 2010 Translational Science Medicine, University of Colorado at Boulder News, Bradley Olwin]

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