Niche for cells
Scientists from Moscow State University have found out why stem cell treatment does not work
Russian biologists have found an explanation for why therapies based on adult stem cells unexpectedly do not cope well with the restoration of the spinal cord and other damaged organs, and have found out how to make them work normally. Their findings were presented in the International Journal of Molecular Sciences (Nimiritsky et al., Unveiling Mesenchymal Stromal Cells’ Organizing Function in Regeneration).
"Great hopes were pinned on stem cells, but the first clinical trials showed that their effectiveness was very low. There were doubts that they could be used at all as "special forces engineers" who could infiltrate any fabric and completely restore it. In reality, they did not turn into the right cells and disappeared after a few weeks," the scientists write.
Over the past two decades, biologists have learned how to turn stem cells into tissues of bones, muscles, skin and the nervous system. These tissues can help with damage to the body or become a cure for a number of degenerative diseases.
Initially, scientists had high hopes for the use of so-called MSC cells to combat such problems. They are adult stem cells present in small quantities in all human organs and have retained the ability to transform into many types of tissues.
Despite the first successes in animal experiments, MSC cells today have acquired a controversial status due to the low efficiency of healing of damaged tissues and their lack of ability to turn into neurons and some other types of cells.
Moreover, a year ago, their discoverers proposed to remove the word "stem" from their name, as it misleads people and promotes the spread of therapies of dubious effectiveness that have not passed a full-fledged blind test.
Pavel Makarevich, head of the laboratory at the Institute of Regenerative Medicine of the Moscow State University, and his colleagues found out how to make MSC cells more actively participate in the regeneration of tissues and organs by studying how they behave inside living connective tissue.
Analyzing the results of their own experiments and the results of observations by other scientists, Russian biologists noticed a curious thing: the behavior of these "special forces cells" changes greatly if you extract them from the environment in which they originally lived.
Makarevich and his colleagues suggested that the niches in which these cells live are similar in their structure to complex ecosystems consisting of several layers of organisms with different ecological roles. Adult stem cells occupy the top of this pyramid, and their full-fledged work depends on all its other steps and those signals that emit other components of connective tissue.
Drawings from an article in the International Journal of Molecular Sciences – VM.
Guided by this idea, the scientists compared how stem cells from different parts of connective tissue behaved. This allowed them to discover that their behavior, as well as the set of signals generated, is quite different.
As Makarevich and his colleagues suggest, some of them form a kind of framework – a support system that feeds the rest of the stem cells and controls their behavior when healing injuries.
Russian biologists have tested this idea in practice, growing not cultures from disparate stem cells, but peculiar multicellular layers that mimic a full-fledged connective tissue in their structure.
The first experiments on the implantation of such cellular "sandwiches" into the body of animals showed that they coped much better with the regeneration of nervous tissue, skin abscesses, ischemia and other diseases that they unsuccessfully tried to eliminate with the help of "ordinary" MSC cells. Scientists hope that such an approach will make adult stem cells a truly effective tool for tissue and organ regeneration in the near future.
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