Organoid Treatment Lowers Inflammation, Fibrosis in Mice

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with stem cells grown into a skin-like structure called an organoid reduced inflammation and fibrosis (scarring) in a mouse model of localized scleroderma, a new study found.

The study, “Application of an iPSC-Derived Organoid Model for Localized Scleroderma Therapy,” was published in Advanced Science.

An organoid is a cellular structure grown in a laboratory and meant to mimic the cellular and physical architecture of bodily organs. Organoids have been broadly used in research applications, and they also may be useful for generating treatments.

Scientists in China created iPSC-derived organoids of skin tissue. An iPSC, or induced pluripotent stem cell, is a type of laboratory-generated stem cell that is “reverse engineered” from another type of cell — usually a skin cell or blood cell. Like other stem cells, iPSCs are able to grow and differentiate into certain cell types if given specific biochemical cues. In this case, the researchers cued the iPSCs to grow into skin-like organoids.

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The researchers determined that about 27% of the cells in their organoids were mesenchymal stem cells, a specialized type of stem cell that can give rise to bone, fat, and muscle. Another 21% of the organoid cells were epithelial cells, which line the surface of the skin. The rest were mainly nervous system cells, such as neurons, glia, and neuroendothelium cells.

Based on the cell composition, the researchers dubbed their model “epithelial and mesenchymal (EM) organoids.”

The team then tested the effects of transplanting these organoids into the skin of mice with localized scleroderma, induced by applying a chemical called bleomycin. In line with modeled scleroderma, bleomycin-treated mice showed elevated inflammation levels and fibrosis in their skin.

The results showed that treatment with the EM organoids significantly reduced inflammatory and fibrotic markers. It also increased levels of signaling molecules that promote the development of new blood vessels in the skin.

The research showed that EM organoids secreted many signaling molecules that promote healthy skin growth, and that the treatment helped to activate stem cells in the skin.

“These results suggest that the potential mechanism of skin tissue repair in [localized scleroderma] mice is to promote injury repair through active factors secreted by organoids,” the researchers concluded.

“This study provides explicit evidence that the application of iPSC-derived EM organoids can promote recovery of scleroderma pathological phenotypes [disease-associated traits] and skin-associated function, revealing a new feasible method for treating scleroderma from the perspective of regenerative medicine,” they said.