The successful transplantation in rats of vascularised intestinal grafts derived from human cells, reported in Nature Communications, is achieved by building the engineered organs on a “living” scaffold. This result could advance possible treatment options for patients with short bowel syndrome, where there is a shortage of organs.
Short bowel syndrome is a disorder in which loss of a portion of the bowel reduces the ability to absorb nutrients. The current treatment is to transplant intestine, but there are a limited number of organs to transplant and the three-year survival rate is low, due to graft failure and cellular rejection. Transplanting engineered intestines produced using patient-derived cells may address these issues, but previous attempts to build these organs using synthetic scaffold have had limited success. Decellularised intestine has been investigated as an attractive alternative scaffold, but to date, the resulting organs have lacked functional vasculature needed to restore nutrient absorption.
Harald Ott and colleagues create a scaffold that can enable both vascularisation and nutrient transfer. The authors remove cells from a portion of rat intestine using a method that preserves the vascularisation of the scaffold. To re-build the absorptive capacity for nutrients, the authors then add back two types of intestinal cells. First, human stem cell-derived epithelium cells are used to create multiple balls of cells, known as mini-gut spheroids, which fuse together on the scaffold with the aid of a silicone tube. After a two-week culture period endothelial cells are added. Nutrient transfer rates were similar to that from native bowel samples taken from rats and four weeks after transplantation into the rat, the bioengineered intestine continued to survive and mature.
The main impact of this work is to generate a scaffold that is well vascularised and that can enable regeneration of endothelial intestinal cells, as is found in the healthy intestine, to enable longer term survival of the grafts. Although the method has not been tested in humans, and the full degree of maturity to match native intestine has not been reached, these technical advances in terms of size and absorption capabilities of the graft provide promise for bioengineered functional intestine grafts.