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- Macrophage in hand: cell reprogramming will accelerate the treatment of wounds and burns
Macrophage in hand: cell reprogramming will accelerate the treatment of wounds and burns
Russian scientists have found a way to "reprogram" the human immune system to accelerate wound healing and create tissue biosimilars. In fact, it is a method of controlling the protective functions of the body using substances secreted by stem cells. The technology will enable the body to recover faster from severe injuries and surgeries. It will also help in the treatment of burns and will be important for transplantology: the method will avoid rejection of artificial organs and ensure the successful integration of implants into the patient's body. For more information about innovations in medicine— see the Izvestia article.
Why reprogram immune cells?
Researchers at Sechenov University have shown that biologically active substances released by mesenchymal stromal cells (MSCs) from human adipose tissue are able to "switch" immune cells from inflammation mode to recovery mode. This approach can become the basis for new anti—inflammatory and regenerative technologies, from treating injuries to creating biological tissue analogues.
From the volunteers' blood samples, the researchers isolated macrophages, cells of the innate immune system that regulate inflammation and healing processes. They can operate in two modes: one supports the inflammatory response, the other stops it and starts tissue repair. How quickly the body switches between these states determines the success of regeneration after injuries and operations, doctors told Izvestia.
To understand how the behavior of macrophages can be controlled, scientists transferred them to a state characteristic of acute inflammation and exposed them to conditioned media — solutions containing substances that secrete MSCs. They were isolated from subcutaneous adipose tissue and grown both on a flat surface and in the form of three-dimensional spheroids, and their maturation time varied.
Observations showed that such conditioned MSCs environments significantly weakened the inflammatory activity of macrophages and facilitated their transition to a recovery mode. The most pronounced effect was given by the medium obtained after 72 hours of cultivation of three-dimensional spheroids.
—Wound healing, soft tissue regeneration, and successful integration of biomaterials depend on how quickly the immune system switches from inflammation to recovery. The use of MSCs secretion products enhances natural recovery mechanisms. This is especially important when creating artificial tissues, where excessive inflammation can interfere with the integration of the construct," explained Timofey Klyucherev, a junior researcher at the Institute of Regenerative Medicine at Sechenov University.
The next stage of research is to study the effect of such environments in more complex models and evaluate their potential for developing biomedical products. According to scientists, the technology can improve the engraftment of biomaterials and increase the efficiency of tissue repair in surgery, dentistry and regenerative medicine.
Where the new macrophage switching technology will help
The rate of tissue healing depends on how quickly macrophages, the key cells of the immune system, switch from an inflammatory response to a regenerative one. If this does not happen, the inflammation drags on, and a scar forms at the wound site, molecular biologist Arina Kholkina explained to Izvestia.
— The technology opens the way to the creation of cell-free drugs for regenerative medicine. Such solutions can be applied to sutures, implants, and added to biopolymer scaffolds in tissue engineering. This reduces the risk of rejection and simplifies production compared to cell therapy. It can be used in surgery, dentistry, wound and burn treatment, wherever rapid and complete tissue repair without chronic inflammation is critically important," she said.
The very idea of "switching" macrophages from pro—inflammatory mode to recovery mode is very promising, because this is an attempt not to roughly turn off inflammation, but to physiologically shift the balance towards healing, Albert Rizvanov, head of the Personalized Medicine Center of Excellence at the Institute of Fundamental Medicine and Biology of KFU, commented on the study.
Unlike classical anti-inflammatory approaches, which often work "head-on" and, if used unbalanced, can increase the risk of complications, secreted MSC factors act more mildly. According to the specialist, this is why such solutions are so in demand where healing, implant integration and fibrosis control are important: in surgery, dentistry, regenerative medicine, and tissue engineering.
— But there is a key limitation here, because of which there are a lot of similar developments in the world, and only a few have reached real clinical practice: standardization of the secretome. The "conditioned medium" is essentially a complex mixture of proteins, lipids, RNA, and extracellular vesicles, and its composition depends on the donor, the original tissue, and many other conditions. Without validated quality control methods and batch reproducibility, the product is difficult to scale and register," the specialist noted.
The work is carried out within the framework of the program "Priority 2030" (national project "Youth and Children") and the megaproject "Organ-to-order".
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