How to improve the survival of MSCs in the recipient's body
Mesenchymal stem cells (MSCs), discovered several years ago, initially seemed to be a very valuable find for regenerative medicine. These cells, isolated from bone marrow and adipose tissue, are able to give rise to cells of bone, cartilage, muscle and other types of connective tissue. However, the results of clinical studies did not justify the hopes of scientists. One of the reasons for this is the short lifespan of transplanted cells in the body.
Harvard University researchers working under the leadership of Dr. Juan Melero-Martin have demonstrated that the results of mesenchymal stem cell transplantation can be improved by simultaneous administration of endothelial colony-forming cells to the recipient. These cells are circulating in the bloodstream precursor cells of the inner lining of blood vessels - the endothelium.
As part of the study, the authors transplanted mesenchymal stem cells isolated from human bone marrow or adipose tissue under the skin of immunodeficient mice in combination with endothelial colony-forming cells isolated from umbilical cord blood. Only mesenchymal stem cells were transplanted into animals of the control group.
An analysis of animal tissues carried out a few weeks later showed that endothelial colony-forming cells significantly increased the survival of mesenchymal stem cells in the recipient's body by suppressing early apoptosis and at the same time ensured the preservation of characteristic features of stem cells, including the ability to repopulate during secondary transplantation.
Fat cells (yellow) that appeared as a result of differentiation of human MSCs (green) in the mouse body
28 days after transplantation. The mouse's own adipocytes are indicated in red, the cell nuclei are indicated in blue.
At the same time, in the absence of endothelial colony-forming cells, only a small number of mesenchymal stem cells took root in the recipient's body.
This can be explained by the fact that in the body mesenchymal stem cells are usually localized in close proximity to capillaries and constantly receive the signals necessary for their functioning. When cultured in the laboratory, cells receive these signals from nutritional supplements introduced into the medium. However, during transplantation, the absence of a sufficient number of capillaries in the injection zone leads to their death.
The authors are already collaborating with colleagues conducting clinical studies of mesenchymal stem cell transplantation methods to restore bone and adipose tissue. However, they recognize that joint transplantation of two types of cells requires additional experiments to determine the safety and effectiveness of the procedure. Another direction of their further work is the identification of signaling molecules obtained by mesenchymal stem cells from endothelial colony-forming cells and the development of methods for their reproduction in the absence of cells.
Article by Ruei-Zeng Lin et al. Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engagement via paracrine signaling published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Harvard University:
Research team pursues techniques to improve elusive stem cell therapy.
03.07.2014