Researchers create functional intestines from stem cells

A team of researchers from the Harvard Medical School have created functional small intestine segments using stem cells.

A stem cell is a cell with the unique ability to develop into specialised cell types in the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. They are different from other cells in the body because they can divide and renew themselves over a long time. They are unspecialized, so they cannot do specific functions in the body, and they have the potential to become specialised cells, such as muscle cells, blood cells, and brain cells.

The researchers bioengineered the segments using human induced pluripotent stem cells (iPSCs), which delivered nutrients into the bloodstream when implanted into rats.

Senior study author and associate professor of surgery at Harvard Medical School, Harald Ott, said in the online journal Nature Communications that through the study, they have been able to bridge the gap between differentiation of single cells, driving stem cells to become specific cell types, and the generation of tissue that shows a higher level of function, in this instance vascular perfusion and nutrient absorption.

He said: “While previous studies have reported successful differentiation of organoids— millimeter-small units of tissue— from iPSCs, we describe a technology that enables these smaller units of tissue to form larger-scale grafts that someday could be used as implanted replacement organs.”

The study utilises a procedure he developed in 2008 for stripping the living cells from a donor organ with a detergent solution and then repopulating the remaining extracellular matrix scaffold with organ-appropriate types of cells.

His team has decellularised animal kidneys, lungs and hearts; generated functional rat kidneys and lungs; and last year, regenerated functional heart muscle in decellularised human hearts.

“Our in vivo experiments showed that human iPSCs differentiated towards an intestinal fate can be assembled into an intestinal graft with a high level of organisation and connected to a recipient’s vasculature to enable nutrient absorption after transplantation,” Ott said.

“The next steps will be to further mature these grafts and to scale the construct to a human size, so that someday we may be able to provide a more accessible alternative to small bowel transplantation for patients with short bowel syndrome—ideally growing ‘on-demand’ patientspecific grafts that would not require immunosuppressive drugs,” he added.