06 November 2014

Recipe for bioengineered organs without stem cells

How to grow a blood vessel

Alexandra Bruter, <url>

A group of scientists from Gothenburg, Sweden, published an article in the EBioMedicine journal (Olausson et al., In Vivo Application of Tissue-Engineered Veins Using Autologous Peripheral Whole Blood: A Proof of Concept Study), which describes how they managed to grow and transplant a new blood vessel to two patients using a donor vessel and 25 milliliters of blood the recipient. Well, and some laboratory reagents.

Poor vascular condition and insufficient blood supply turn out to be the cause or a markedly decreasing quality of life consequence in many pathologies.

Firstly, the narrowing of the lumen of the coronary vessels (supplying blood to the heart) leads to heart failure, angina, etc. The ingestion or formation of a blood clot in them leads to myocardial infarction at all. Currently, aorto-coronary bypass surgery and stenting are used to improve coronary blood supply. Aorto-coronary bypass surgery in 2011 turned out to be the most frequent operation performed in the United States (1.4% of the total). When shunting from somewhere, usually from the leg, a fragment of a vein with doublers is cut out and sewn with one end to the aorta, and the other to the coronary vessels below the place where the obstruction formed in them. After that, part of the oxygen-enriched blood flowing from the heart into the aorta will immediately enter the coronary vessels and nourish the heart muscle. Stenting is a manipulation in which a hollow expander cylinder is inserted into the lumen of a narrowing vessel, which does not allow the vessel to narrow completely. Unlike aorto-coronary bypass surgery, a complex open–heart surgery with all its risks and the difficulty of subsequent recovery, a stent is installed through the femoral artery, and the patient does not even have to be given anesthesia.

Another disease associated with insufficient blood supply is diabetes mellitus. With diabetic angiopathy, the vessels become more brittle, the likelihood of atherosclerosis and thrombosis increases. The blood supply is deteriorating. All this is especially characteristic of small vessels of the lower extremities. In combination with other manifestations of diabetes, this leads to the development of the so-called diabetic foot syndrome, often ending in amputation.

In general, for the aging and plumping population of developed countries, the problems of poor blood supply are very relevant for a variety of reasons.

In the work we are talking about, the portal vein of the liver was prostheticized. The portal vein is not a vein in the literal sense of the word, blood does not flow through it to the heart. The portal vein collects blood coming from the organs of the gastrointestinal tract and spleen, and directs it to the liver. In some cases, due to thrombosis or developmental abnormalities, the portal vein may be impassable or simply absent.

Patients who participated in the study were admitted to the hospital with complaints of fatigue, abdominal pain. Both girls (one four, the other one and a half years old) lagged behind in growth and weight gain. In one of them, the painful sensations were clearly associated with eating. The blood test revealed anemia, thrombocytopenia, neutropenia, but the diagnosis was not hematological. Computed tomography showed the absence of portal vein in both girls.

Sometimes in such cases, a new vein is made from the umbilical artery. The umbilical artery during intrauterine development connects the child's body with the mother's body, after birth it becomes unnecessary and is gradually reduced, its lumen overgrows. In some cases, its remnants can be used for prosthetics of the portal vein, but in this case nothing remains of the umbilical arteries. You can also try to transplant donor vessels, and in rare severe cases, the whole liver, but this will mean the risk of rejection and lifelong use of immunosuppressive drugs.

Since these options do not exhaust all cases of pathology, methods for manufacturing artificial personalized vessels have been developed. In the early stages of technology development, they tried to use tubes made of inorganic materials, populating them inside with cells or waiting for the vascular endothelium to germinate into an artificial vessel at the contact points. This approach has not been successful.

In their previous work, the authors proposed a more promising approach. It is impossible to transplant a donor vessel – it will cause an immune response. It is also impossible to make a new vessel from cells in a test tube – cells cannot be so easily persuaded to form a three-dimensional structure of a vessel or any other organ. But in recent years, a new approach has been actively explored, consisting in the use of a cell-free matrix. We used to write about the heart valve and mentioned the mouse kidney created in this way.

Cells are washed out of the donor tissue or organ with special solutions, and all DNA is destroyed. Only a three-dimensional framework of intercellular substance remains. This framework is populated with new cells. Such a design should not cause an immune response, because it contains only recipient cells.

In the first experiment, the skeleton of the future portal vein was populated with the help of stem cells from the bone marrow. They can differentiate into both vascular muscle cells and endothelial cells lining the vessel from the inside. There are downsides to this approach. Firstly, bone marrow puncture is a painful procedure. Secondly, stem cells need to be propagated in culture for a long time. This takes time and increases the risk of genetic aberrations.

The authors of the work found that you can do without stem cells. The circulating blood carries a sufficient number of endothelial cells, and 25 milliliters was enough for the primary settlement of the vessels. Vessels were transplanted to two patients, and another patient was previously transplanted with a vessel populated with stem cells.

Only in one of the three cases there were complications, one of the girls had a blood clot in a new vessel. The operation had to be repeated.

To date, more than a year and a half has passed since the intervention. Blood flow has recovered, well-being according to parents' estimates and objective indicators has improved. The experiment can be considered quite successful.

The blood vessel and the heart valve have a relatively simple three-dimensional structure and consist of a small number of cell types.

However, there is hope that in the future, the cell-free matrix technology will allow the creation of more complex organs from recipient cells. This will greatly advance the whole transplantology, which is currently severely limited by the shortage of donor organs and the compatibility problem.

Portal "Eternal youth" http://vechnayamolodost.ru06.11.2014

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