Synthetic stem cells could help reverse heart failure
March 6, 2017
In many ways, the heart is like a tire. Its elastic walls handle immense pressure, and work tirelessly to keep the rest of the body moving. Like a tire, the walls of the heart can wear down over time, the elastic does not spring back as readily as it used to and the tire cannot hold up to the high pressure the way it did when it was new.
That wearing out of the heart wall is what we know as heart failure: the stretching, weakening and buildup along the heart wall that keep the heart from pumping enough blood to the rest of the body. Like a tire, there are ways to fix a heart. Just as you can patch a tire, you can replace valves or administer a bypass on a heart. People change out tires all the time, when a patch isn't enough. And while it is far less common, people can also get new hearts via transplant.
Now researchers from the University of North Carolina, NC State University and Zhengzhou University in China are adapting stem cell technology to create a therapy that could revitalize the muscles in the heart wall—putting the spring back into the tire rubber. In test tubes and in mice, the treatment improved heart function, increased the amount of healthy heart tissue and decreased the size of scarring. The research was published in the journal Nature Communications.
The researchers injected heart tissue with synthetic, lab-made stem cells. Ke Cheng, a biomedical engineering professor with dual appointments at NC State and UNC, says that these “cell-mimicking microparticles” (CMMPs) perform most of the regenerative functions of real stem cells, but they are less risky than real stem cells and can be more easily stored for later use.
Stem cells are cells that have yet to undergo the full process of differentiation—cells that can become other types of cells. The goal of stem cell therapies, otherwise known as regenerative medicine, is to inject these blank canvas cells into diseased or injured organs so that healthy new cells can replace the injured or dead ones. Previous clinical trials have shown that stem cells can help regenerate tissue in diseased human hearts and decrease the chances of hospitalization and death in patients with severe heart failure over a 12-month period.
Previous research, however, has shown that most of the benefit from stem cell therapy does not actually come from the stem cells replacing damaged tissue. Instead, the stem cells release signaling molecules called paracrine factors that help the damaged tissue repair itself.
Further, stem cell therapies have risks. Stem cells are supposed to mature and divide to create healthy new cells, but if that division goes out of control, it can turn into cancer. This side effect has mainly been reported in mice, as opposed to larger animals like humans, but it is still a possibility.
Cheng’s CMMPs package the proteins that make the paracrine factors and a biodegradable polymer inside the cell membrane of cardiac stem cells. The membrane gives them the ability to slip into the heart without setting off the immune system while the proteins inside make the paracrine factors that heal surrounding heart tissue. The CMMPs, however, are missing the DNA and molecular machinery that would allow them to reproduce so there is no possible risk of cancer.
In test tubes, when CMMPs were mixed with heart cells from newborn rats, the CMMPs attached to the heart cells and promoted healthy contraction of the rat heart tissue almost as well as real cardiac stem cells.
In mice that had had heart attacks, the CMMPs improved the ejection fraction—the percentage of blood the heart is able to pump out of itself with every beat—after a four-week period. Compared to a placebo, the CMMPs doubled ejection fraction, nearly quadrupled the amount of working heart muscle and cut the scar size in half. In each of those tests, CMMPs fell just short of real cardiac stem cells.
The function trials were performed in mice without fully functioning immune systems as a mouse immune system will attack human stem cells. When the researchers gave CMMPs to mice with full immune function, very few immune cells migrated to the heart.
Further, the CMMPs stayed mainly in the heart, with a few cells flowing through the heart to the lungs or liver. This is beneficial because it shows the CMMPs stay where they are needed in the heart without causing excess growth where it isn’t needed.
Cheng says CMMP treatments have broad potential in regenerative medicine. Since CMMPs simply borrow proteins and cell membranes, they can be adapted to any type of stem cell that works in any part of the body. Beyond that, live cells do not keep for very long, so stem cell therapy requires harvesting fresh cells every time. CMMPs, on the other hand, are just polymers and proteins, and they can be frozen, kept and thawed without harming them, so a CMMP treatment could potentially be stowed and used whenever they are needed.
This study examined only mice and CMMPs are still many years from becoming a treatment that is found in every hospital. Still with clinical trials of real stem cells slowly but surely making progress, the next generation of regenerative therapy could be close behind.
Daniel Lane covers science, medicine, engineering and the environment in North Carolina.