‘Miniguts’ from human pluripotent stem cells with functional nerves – a milestone in regenerative medicine 

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This image from the study published by Nature Medicine shows human intestinal organoids with enteric (intestinal) nerves that were generated in a petri dish using human pluripotent stem cells (hPSCs). hPSCs can become any cell type in the body.
This image from the study published by Nature Medicine shows human intestinal organoids with enteric (intestinal) nerves that were generated in a petri dish using human pluripotent stem cells (hPSCs). hPSCs can become any cell type in the body. The nerves can be seen as the white fluffy cloud around the dense tissues. Source: Nature Medicine, press release

In a groundbreaking study at the Cincinnati Children’s Hospital Medical Center led by Michael Helmrath and Jim Wells, scientists have reported success in developing intestinal tissue with a functional enteric nervous system. It was further used to study Hirschsprung’s disease, a genetic condition in which the colon lacks nerve cells, that leads to complications in passing stool.

The gastrointestinal tract contains the second largest number of nerves in the human body, according to Wells. When they are absent or not functional, or when these nerves fail to work properly – the contractile movement of intestinal muscles is hindered. This contributes to abdominal pain, diarrhoea, constipation, and in severe cases creates functional blockages that require surgery.

Why is this exciting?

The novelty of this study was the incorporation of neural development in three-dimensional lab-grown intestinal tissues from human pluripotent stem cells (method published by Well’s group). Neural crest cells manipulated to form enteric nerves were added to the developing tissue, although – the when and how to mix the two – were the biggest challenges to the team.

“We tried a few different approaches largely based on the hypothesis that, if you put the right cells together at the right time in the petri dish, they’ll know what do to. It was a longshot, but it worked,” said Wells, who credits Cincinnati Children’s developmental biologist Samantha Brugmann, PhD, (and a study co-author) with providing critical insights into embryonic nerve development.

The resulting tissue had a remarkable semblance to the developing fetal intestine and demonstrated robust growth, nutrient processing and notably peristalsis (the rhythmic contractions of the intestinal muscles that allow food to pass through) when transplanted into mice.

Therefore, the first of its kind, this tissue derived by combining human pluripotent stem cells and neuronal precursors looks promising in terms of better integration, development, and functionality. According to the authors, these findings take us one step closer to engineering patient-specific human intestine and offer huge advantages in the field of regenerative medicine.

How can functional organoids improve regenerative medicine?

Firstly, such functional organoids developed from patients’ cells allow clinicians to understand the particular disorder in a lab setup and test new drugs or side effects non-invasively before actual administration in the patient. Further, genetically modified (rectified in case of congenital genetic disorders) versions of their tissues can be grown for transplant.

“One day this technology will allow us to grow a section of healthy intestine for transplant into a patient, but the ability to use it now to test and ask countless new questions will help human health to the greatest extent,” said Michael Helmrath, surgical director at the Intestinal Rehabilitation Program at Cincinnati Children’s.

This is an exemplary study that combines basic research and its clinical applications in congenital intestinal disorders. Despite the questions on ethics and restrictions this technology might face, one cannot deny the endless possibilities it opens up in engineering personalized organs from biopsies for patients with specific conditions.

The original article was published in Nature Medicine.

Sources: Futurism, Cincinnati Children’s Newsroom