Stem cell researchers closer to creating human organs
Researchers in the US have made functional intestinal tissue in the lab that could be used to test new drugs and – in time – even be transplanted into patients to correct gastrointestinal diseases.
The team from Cincinnati Children’s Hospital Medical Centre used stem cells to grow the intestinal ‘organoids’ – structure resembling whole organs or tissues that self-organise into three-dimensional arrangements.
Reporting their findings in Nature Medicine, the scientists led by Michael Helmrath described how they took pluripotent stem cells from adult skin and blood samples and stimulated them with a “molecular cocktail” to encourage them to develop into intestinal cells.
The resulting organoids were then transplanted into mice, positioned underneath the fibrous membrane or capsule surrounding the kidney, which both protected the cells and ensured they were close to a rich blood supply.
Crucially, the transplanted organelles were able to develop and mature within the mice, which had been genetically modified to accept human tissue without causing an immune response. Each mouse in the study produced significant amounts of fully functional, fully human intestine, including differentiated cells in the mucosal lining and muscle layers.
Additional studies showed the organoids were able to carry out digestive functions, such as taking up nutrients, and also responded to simulated, molecular ‘signals’ from the host mouse. Showing that degree of functionality represents something of a breakthrough in the emerging field known as regenerative medicine, which involves using cells or tissues to treat diseases.
“These studies support the concept that patient-specific cells can be used to grow intestine,” said Helmrath, noting that in time patients could receive transplants of intestinal tissue – derived from their own stem cells – that could treat “the many diseases and conditions that can cause intestinal failure.”
These therapeutic applications are likely to be many years away, but in the meantime the organoids could have a near-term role in the study of GI diseases and the discovery of new drug compounds.
Lab-grown organoids have the potential to replace much of the animal testing stage by allowing early drug research to occur directly upon human tissue. Going straight to human tissue testing could shave years off the drug development process, the researchers said.
The discovery marks an ongoing trend among researchers to use cells to create organoid cultures that can be used in drug discovery, tapping into the ability of pluripotent stem cells to generate just about any type of cell type. Other teams have shown that kidney, brain, retina and liver-like tissue can be made in the lab
Last month, researchers also reported in Cell how they created prostate cancer organoids from circulating tumour cells that retained the same characteristics of tumours in patients, while another group recently created a functional, in vitro model of the neuronal degeneration seen in Alzheimer’s disease.
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