When we developed the ability to convert various cells into a stem cell, it held the promise of an entirely new type of therapy.
However, the Nobel Prize for induced stem cells was handed out over a decade ago, and the therapies have been slow to follow.
But a group of German researchers is now describing tests in primates of a method of repairing the heart using new muscle generated from stem cells.
This is a somewhat surprising problem, as it was hoped that using stem cells derived from the same animal would avoid any immune response.
At that point, we’ll be in a better position to evaluate whether stem cells are really ready to live up to their potential.
A whole new kind of treatment seemed possible when we discovered how to turn different cells into stem cells. We could turn a small number of adult cells into stem cells and cause them to form any tissue in the body instead of causing the body to attempt to repair itself with its own cells or deal with the difficulties of organ transplantation. With a practically limitless supply of a patient’s own cells, we might be able to replace or repair tissues.
But since induced stem cells were awarded the Nobel Prize more than ten years ago, treatments have been sluggish to emerge. However, a team of German researchers is now reporting on experiments in primates regarding a technique for heart repair that uses stem cell-generated muscles. Although the results do not yet meet our expectations, they are encouraging. But they have been sufficient to initiate clinical trials, and human subjects are showing comparable outcomes.
heart issues.
Many specialized tissues, such as those that form blood vessels or are experts at conducting electrical signals, are found in the heart. A type of specialized muscle cell known as a cardiomyocyte, however, is essential to the heart. A fixed population results from the cardiomyocytes’ cessation of division upon heart maturity. Damage will accumulate because the heart cannot be repaired from injuries or infections.
This can repeatedly deprive large regions of the heart of oxygen and nutrients, killing the cardiomyocytes there. This is particularly problematic when blood vessels are blocked. As a result, cardiac function declines and may eventually lead to death.
Induced pluripotent stem cells (IPSCs), which are pluripotent—meaning they can develop into any type of cell—can be converted rather easily, it turns out. In the hopes that they would be assimilated into the injured tissue, researchers attempted to inject these stem-cell-derived cardiomyocytes into experimental animals’ injured hearts. However, the benefits of these experiments to the animals were not always evident.
In Germany, the team tried a slightly different strategy. Instead, they produced a layer of cardiomyocytes and a distinct layer of stroma, a mixed population of cells that make up the connective tissue and blood vessels that support cardiomyocytes in mature hearts. These two cell sheets were joined to form a single patch that could be affixed to the outside of the heart.
This improved heart function in mice used in experiments. Before beginning human trials, the team sought advice from a German research ethics body on which large animal to use for additional testing. Macaques were the response that was returned.
Good things.
On Wednesday, the results of the macaque work and one human heart from the subsequent clinical trial were published in a paper. After the patient to whom the heart belonged underwent a transplant, his stem-cell-treated heart could be examined. Additionally, in addition to controls, the researchers treated a variety of macaques with varying-sized cell patches.
A basic characterization of the patches’ post-implementation fates comprises the majority of the work, which addresses many of the possible issues related to introducing a significant quantity of tissues derived from stem cells into an adult animal.
This is good because there are a few major concerns that don’t appear to be problems at all. Firstly, it’s possible that immature stem cells are still present among mature cardiomyocytes and could develop into tumors. This instance did not show that. Another concern is that the extra tissue might not be able to properly integrate into the hearts. People were worried that instead of cooperating with the heart, cardiomyocytes in culture would continue to beat to their own rhythm once they began to contract on their own. However, none of the animals that received transplants showed any symptoms of arrhythmias, indicating that the sheets of cells that were implanted had blended in with their environment.
However, the implants were not without issues. First of all, some of them developed cells from the bone/cartilage lineage, indicating that some stem cells in the sheets had not yet committed to a mature state.
An additional issue is that, even though the animals were given immunosuppressive medications, one of them developed an immune reaction to the implanted cells. It was hoped that using stem cells from the same animal would prevent any immune response, so this is a somewhat unexpected issue. It goes without saying that this will require more investigation.
But the grafts appeared to be effective. Increased heart wall thickness and contraction resulted from the grafts, and the grafted hearts circulated more blood.
Some questions remain.
However, it appears that the implants are not comparable to the heart tissues they are intended to replace. Although the cardiomyocytes in the implant sheets were mature, their size was not as great as that of the mature heart. That might have something to do with another problem: The implants didn’t completely integrate into the heart’s blood supply. There are possible solutions for this; several signaling molecules that promote blood vessel formation have been found. Nevertheless, further research in animals will be necessary to test them, which might also enable us to determine whether a larger cardiomyocyte is a result of improved blood flow.
The one human heart that could be analyzed, meanwhile, yielded findings that matched those found in the macaques. However, once the complete trial data is available, we’ll be able to determine whether that is the usual outcome. We will then be in a better position to assess whether stem cells are truly prepared to fulfill their potential.
20225 Nature. 10.1038/s41586-024-08463-0 (About DOIs) is the DOI.
