Endothelial cells will help to repair the organs
Vascular endothelial cells can repair organs
LifeSciencesToday based on materials from Weill Cornell Medical College:
Blood Vessel Cells Can Repair, Regenerate Organs, Say Weill Cornell ScientistsAccording to the scientists of the Cornell Medical College of Vail (Vail Cornell), damaged or diseased organs can be restored by the introduction of blood vessel cells, without resorting to transplantation of donor organs.
In articles published in the journals Stem Cells (Israely et al., Akt suppression of TGFb signaling contributes to the maintenance of vascular identity in embryonic stem cell-derived endothelial cells) and Developmental Cell (Nolan et al., Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration) researchers have shown that endothelial cells, which make up the structure of blood vessels, are powerful biological mechanisms that control tissue regeneration through the release of organ-specific molecules.
Scientists have decoded the entire volume of active genes of endothelial cells, finding hundreds of known genes that have never been associated with these cells. Moreover, they came to the conclusion that the structure and functions of blood vessels, including the repair molecules secreted by them, are determined by the organs themselves.
Eliminating damage and restoring function, endothelial cells and the organs into which they are transplanted work together, explains the head of the study Shahin Rafii, MD, professor of genetic medicine and co-director of the Ansari Stem Cell Institute and the Tri-SCI Stem Center. "If an organ is injured, its blood vessels cannot repair the damage on their own, because they themselves can be damaged or inflamed."
"Our work shows that engineered endothelial cells can take root in damaged tissue and acquire the ability to repair an organ," continues Dr. Rafii, a researcher at the Howard Hughes Medical Institute. "These studies, combined with the first atlas of molecules of organ–specific blood vessel cells, presented in an article in Developmental Cell, open up a whole new chapter in translational vascular medicine and will find the widest therapeutic application. Scientists considered the blood vessels of all organs to be the same, and their only function was the delivery of oxygen and nutrients. But they are very different, and each organ is endowed with blood vessels with a unique shape and function that solve the difficult task of meeting the metabolic needs of this particular organ."
In a study published in Developmental Cell, scientists studied nine different tissues in a state of homeostasis – a stable, healthy state – as well as liver and bone marrow recovering from traumatic injury.
Having developed a technique that made it possible to obtain pure populations of endothelial cells in a very short period of time, they were able to identify all the genes of these cells expressed in different populations. It turned out that endothelial cells possess tissue-specific genes encoding unique growth factors, adhesion molecules and factors regulating metabolism.
"We knew that these gene products are essential for the health of a particular tissue, but before our study there was no understanding that the source of these factors are endothelial cells," says lead author of the article in Developmental Cell Dr. Daniel Nolan (Daniel Nolan), senior researcher at the laboratory of Raffia.
"In addition, we found that tissue regeneration in the liver and bone marrow proceeded unexpectedly differently - including repair molecules known as angiocrine growth factors expressed by endothelial cells," adds Dr. Olivier Elemento, who performed complex computer calculations for the study.
"There are different blood vessels in different organs, because endothelial cells must constantly adapt to the metabolic, biomechanical, inflammatory and immunological needs of a particular organ," says Dr. Michael Ginsberg, a postdoctoral fellow in Dr. Rafia's laboratory. "And now we have established how endothelial cells have learned to behave differently in different organs and adapt to their needs."
These discoveries raise the question of how endothelial cells adapt to the biological needs of each organ. Is it possible to create "immature" endothelial cells that would help scientists find the means by which microenvironment signals would "teach" cells how to become more specialized?
In search of answers to this question, scientists have suggested that endothelial cells derived from embryonic stem cells can behave like flexible endothelial cells that can be trained to function the way organ-specific blood vessel cells do. This assumption was confirmed: from mouse embryonic stem cells, the researchers obtained functional, transplantable and endothelial cells that respond to microenvironment signals.
Clusters of transcription factors, angiocrine growth factors, adhesion molecules and chemokines
they are expressed by the endothelial cells of each organ in unique combinations.
(Fig. Developmental Cell)Endothelial cells derived from embryonic stem cells "are universal, and therefore they can be transplanted into various tissues, can be "trained" by the tissue and acquire the characteristics of native endothelial cells," explains senior author of the article published in Stem Cells, Dr. Sina Rabbany, associate professor of genetic medicine and bioengineering Vail Cornell.
According to Dr. Rabbani, such cells can be obtained in large quantities in the laboratory. "Now we know what it takes for these cells to be healthy, stable and suitable for transplantation," says the scientist.
Indeed, in a study published in Developmental Cell, scientists transplanted universal endothelial cells obtained by Dr. Rabbani's group into the liver of mice and observed that they became indistinguishable from the organ's own endothelial cells. The same thing happened when the cells were transplanted into the kidneys.
"These naive endothelial cells acquire the phenotype – the molecular profile and signature – of native endothelial cells as a result of exposure to the unique microenvironment of a particular organ," explains Dr. Ginsberg. "Transplanted endothelial cells are trained by the unique biophysical microenvironment of the organ in which they are placed. They transform into endothelial cells that belong to this organ and that can restore it."
"If you have a heart disease and you need to restore some of your cardiomyocytes, the endothelial cells located in the heart secrete specific factors that allow the heart to recover," Dr. Rabbani adds to his colleague.
However, in order to be used in clinical practice, endothelial cells must be immunocompatible with the recipient's body.
"Endothelial cells can be obtained from human pluripotent embryonic stem cells, as well as by somatic cell nucleus transfer," says study co–author Dr. Zev Rosenwaks, director and chief physician of the Ronald Perelman and Claudia Cohen Center for Reproductive Medicine.
"The somatic cell nucleus transfer method consists in introducing the somatic cell nucleus into a human egg, resulting in the formation of embryonic stem cells. The endothelial cells obtained from them are genetically compatible with the patient's body," explains Dr. Daylon James, associate professor of reproductive biology at Vail Cornell, who made a great contribution to the development of protocols for obtaining endothelial cells from human embryonic stem cells.
In addition, in order to remove from the agenda questions about bioethics related to human embryos or eggs, and about the potential predisposition of embryonic stem cells to the formation of cancerous tumors, it is possible to take cells simply discarded after prenatal diagnostic amniocentesis and reprogram them into endothelial cells capable of regenerating blood vessels. Freezing and creating a reserve fund of such cells will allow them to be transplanted to different patients from a genetic point of view, adds Dr. Rosenwaks, referring to the work (Efficient Direct Reprogramming of Mature Amniotic Cells into Endothelial Cells by ETS Factors and TGFb Suppression), published last October in the journal Cell. The author of this technique is Dr. Ginsberg.
Before clinicians can start testing endothelial cell transplantation, additional preclinical studies are needed, but, according to Dr. Rafia, the therapeutic potential of endothelial cell transplantation is absolutely limitless.
"They can be used as a Trojan horse to block tumor growth, as well as modified in such a way that they can carry toxic chemicals. They can become biological multifunctional cruise missiles aimed at diseased organs," the scientist believes. "Our work is just beginning."
Portal "Eternal youth" http://vechnayamolodost.ru14.10.2013