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Cultivation of stem cells in the laboratory will overcome the immune rejection of organs
Last reviewed: 23.04.2024
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A study of scientists from the Southwestern Medical Center of the University of Texas (University of Texas), just published by Cell Press in the journal Cell Stem Cell, can help in developing more promising therapeutic strategies for transplantation of hematopoietic stem cells. Preliminary cultivation of these cells in the laboratory for about a week may allow one to overcome one of the most difficult obstacles to successful transplantation - immune rejection.
Hematopoietic stem cells (hematopoietic stem cells, HSCs) are cells that give rise to all types of blood cells. Hematopoietic cell transplantation is used to treat leukemia, lymphoma and other types of cancer, as well as autoimmune diseases.
Bone marrow. Light micrograph of stem cells, which give rise to blood cells. White blood cells - large, purple, red blood cells - pale, platelets - small purple granules. Blood cells are constantly formed in the bone marrow, as the life span is very short. Red cells, platelets and all three types of white cells (granulocytes, lymphocytes and monocytes) originate from one ancestral cell - the multipotent stem cell. (Photo: Astrid & Hanns-Frieder Michler / Science Photo Library, P234 / 0030)
However, the lack of understanding of the interaction between hematopoietic stem cells and the immune system of the recipient organism greatly complicates both stem cell research and the development of practical transplantology. There is a significant risk that transplanted cells will not be accepted by the host organism, that is, new cells will be torn away by its immune system. Among the main problems of allogeneic transplantation are a low level of engraftment of donor transplants and a high risk of life-threatening graft-versus-host disease. Transplantation of purified allogeneic HSC reduces the risk of the latter, but leads to a reduction in engraftment.
Although scientists know some of the reasons for such failures, many questions remain unanswered. "Solving these problems will contribute to an understanding of the immunology of hematopoietic stem cells and other stem cells and significant progress in practical transplantology," said research director Dr. Chen Cheng Zhang.
Dr. Zhang and his colleagues have already proved that human and mouse hemopoietic stem cells (HSC) can be successfully grown in the laboratory and then used for transplantation. At the same time in many proteins expressed on the surface of such cells, there are certain changes. Scientists are interested in whether such an "out-of-body experience" can change the functional properties of HSC and make them more suitable for transplantation.
Transplantologists are especially interested in clinically significant allogeneic transplants, that is transplantations between genetically different individuals, including siblings and unrelated donor / recipient pairs. Dr. Zhang's group transplanted both the newly isolated HSCs and GSK grown in the laboratory to mice, and found that cells that had been "spent" in the laboratory for about a week were much less likely to conflict with the immune system of the recipient's body. Ex vivo mouse hematopoietic stem cells successfully overcome the barrier of the main histocompatibility complex and colonize the bone marrow of allogeneic recipient mice. The use of an eight-day culture results in a 40-fold increase in the ability of allografts to be engrafted.
The researchers decided to study the mechanism underlying this effect in more detail and found that both the increase in the number of HSCs and the culture-induced enhancement of cell surface expression of a specific inhibitor of the immune system CD274 (B7-H1 or PD-L1) contributed to this increase.
"This work should shed new light on understanding the immunology of hematopoietic stem cells and other stem cells and can lead to the development of new strategies for successful allogeneic transplantation," Dr. Zhang concludes. "The ability to replicate donor human HSCs in culture and transplant them to people genetically distant from donors, while avoiding the development of the" graft versus host "reaction, will be the solution to the underlying problem in this area."
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