Biologists have grown human intestines in rats
Anna Obraztsova, N+1
Biologists from Massachusetts General Hospital in Boston managed to grow fragments of human intestines inside the body cavity of a rat. The fragments turned out to be functional – they absorb nutrients and transfer them to the blood. The work was published in the journal Nature Communications (Kitano et al., Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts).
Some serious diseases of the digestive system lead to the patient having part of the intestine removed. This happens, for example, in Crohn's disease, malignant intestinal formations and enteritis. Sometimes, after the removal procedure, patients can eat in the usual way, but adhering to a special diet. However, in most cases, nutrients partially or completely have to be received intravenously. There are not enough intestinal donors for everyone in need of a transplant, so the problem of growing transplants is of particular interest to scientists.
The authors of the new work used a common approach to create artificial organs. They took a four-centimeter sample of rat jejunum and removed cells from it, leaving only the intercellular matrix. It is used as a scaffold (a three-dimensional medium for cell culture), which is populated by human cells.
Since to create a fragment of the intestine, it is necessary to grow not only the lining tissue, but also the vascular tissue, the scientists used two types of cells. To recreate the actual lining layer, the scaffold was populated with precursor cells of intestinal epithelial cells. They were grown from induced stem cells (iPSC), which receive "reversing" the differentiation of ordinary human cells. To recreate not only the lining, but also the blood vessels, after colonizing the scaffold with endotheliocytes, scientists added a second type – endothelial cells. These cells were placed in channels in the scaffold corresponding to arteries and veins.
A fragment of the intestine with fluorescently colored cells (red – endotheliocytes, green – epithelial cells). Drawing from the Mass press release. General team creates functional, stem-cell-derived small bowel segments.
The authors began testing the resulting fragment of the intestine by checking its operability ex vivo, that is, outside of a living organism. They passed solutions containing glucose and fatty acids through the intestinal cavity and measured changes in the level of these substances in blood vessels. The result was compared with an intestinal sample obtained from a recently deceased rat (to simulate a traditional transplant). It turned out that the level of glucose transfer into the blood is 54 percent of the result of a normal intestinal sample, and in the case of fatty acids does not differ at all.
The second stage of verification was an in vivo study – the resulting fragment was implanted in a rat. The researchers connected his arteries to the carotid artery, the veins to the jugular vein, and a nutrient solution containing glucose was again fed into the cavity of the fragment. After feeding the solution, the glucose level in the rat's blood increased, which indicates the functionality of the graft in a living organism.
"Our in vivo experiment has shown that human iPSC differentiated into intestinal epithelial cells can be used to assemble intestinal implants that will have a high level of organization and are connected to the recipient's circulatory system, allowing to receive nutrients" – says Harold Ott, the head of the study. According to him, the next step will be scaling such transplants to sizes suitable for humans.
Last year, American scientists grew intestinal tissue from stem cells that has a nervous system and is capable of independent peristalsis. She had an inner lining that absorbed nutrients and produced digestive juices, fully working muscles and nerves that controlled their undulating contractions.
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