Rejuvenation of the bone marrow niche against aging
As a person ages, so do his hematopoietic stem cells (HSCs), whose function is to form all types of blood cells. This is associated with an increased risk of decreased immunity and the development of certain types of cancer of the hematopoietic system.
Researchers at the University of Ulm, Germany and the Cincinnati Children's Clinic, USA, working under the guidance of Dr. Hartmut Geiger, have found that the aging of the bone marrow niche, which ensures the vital activity of hematopoietic stem cells, also contributes to this problem. They proposed a method of rejuvenation of the bone marrow niche, potentially able to strengthen the immunity of older people and prevent the development of certain types of cancer.
In experiments on mice, the authors analyzed the features of the formation and viability of cells inside and in the immediate vicinity of the bone marrow microenvironment. One part of the experiments was devoted to the study of the formation of stromal cells of the soft shell of the bone marrow (internal periosteum), which forms a thin layer of connective tissue on the inner surface of the bones. The second part of the experiments was devoted to monitoring the levels of osteopontin, a protein synthesized by osteoblast cells forming bone tissue, and other proteins associated with various cells during bone marrow aging.
The image shows a section of the spongy femur of a young mouse stained by immunofluorescence. Red staining indicates the presence of a large amount of osteopontin in the bone and the internal periosteum of the bone marrow cavity, which is important for maintaining a healthy microenvironment of hematopoietic stem cells. The nuclei of cells are colored blue.
The researchers claim that they observed a decrease in the production of osteoblasts and other stromal cells of the inner periosteum of aging mice. They also registered a decrease in the levels of osteopontin in the bone marrow of old animals, which, according to their observations, was associated with a decrease in viability and extinction of the functions of hematopoietic stem cells.
As part of the next series of experiments, the authors transplanted bone marrow cells from old (19-21 months) mice to young (8-10 weeks) animals. At the same time, cells previously treated with a recombinant form of osteopontin were transplanted into parts of the animals.
When transplanted to young animals, the behavior of aging hematopoietic cells acquired the character of the behavior of younger cells. This included a decrease in the relative number of hematopoietic stem cells with a high potential for the formation of various types of blood cells, the ratio of which shifted towards an increase in the populations of T and B lymphocytes and a decrease in the production of myeloid cells.
In addition, the authors demonstrated that treatment with osteopontin rejuvenated aging hematopoietic cells and restored their ability to give rise to various blood cells. This was also accompanied by suppression of signals mediated by the Cdc42 protein associated with aging of hematopoietic stem cells.
As we age, the concentration of osteopontin decreases not only in the bone marrow niche, but also in the general blood flow. Currently, in experiments on mice, the authors are studying the possibility of using osteopontin as a replacement therapy that neutralizes the detrimental effect of an aging bone marrow niche on hematopoietic cells.
Article by Novella Guidi et al. Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells published in The EMBO Journal.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on Cincinnati Children's Hospital: Scientists Wage Fight Against Aging Bone Marrow Stem Cell Niche.
13.03.2017