Study: Organ development modeled by activating signaling pathways in embryos

Scientists at the RIKEN Center for Biosystems Dynamics Research have imitated the formation of organs in a lab by ‘hacking’ signaling pathways that guide the development of connective tissues in the embryo.

According to a release by RIKEN, they mimicked the development of organs in a lab by manipulating signaling pathways that guide the formation of connective tissues in embryos, which support the formation of organs such as the liver and gut. In addition to shedding light on organ development, the study could eventually enable doctors to provide personalized treatments for patients, the study stated.

The formation of visceral organs is primarily led by embryonic epithelial cells, which line surfaces in the body, with close communication from mesenchymal cells that eventually give rise to the circulatory system, skeleton and connective tissues, the study stated. Mesenchymal cells in various regions of the embryo provide specific instructions to the epithelial cells, which form different organs.

“Mesenchymal niche cells maintain epithelial stem cells, and the mesenchymal tissue structure influences the fates of epithelial cells,” RIKEN researcher Mitsuru Morimoto stated.

In 2020, a team led by Aaron Zorn at Cincinnati Children's Hospital analyzed gene expression in the developing gut and found specific signaling pathways active early in embryonic development and give rise to mesenchymal lineages associated with different organs. Using their knowledge, Morimoto and Zorn developed a laboratory protocol that selectively activated the pathways to convert human stem cells into various mesenchymal lineages. The scientists were able to generate mesenchymal subtypes that give rise to the liver, gastrointestinal tract, or respiratory tissues in just one week of cell culture. Keishi Kishimoto, a researcher from Morimoto’s group, said the group is eager to apply this approach in the context of regenerative medicine by generating models of human congenital diseases using patient-derived stem cells.

Kishimoto and Morimoto plan to use 3D cell-culture models called "organoids" to understand how the genetic mutations derail developmental processes. First, they will look at tracheoesophageal fistula, a rare condition where the esophagus and windpipe are fused together, which can create respiratory issues. They will then create tracheoesophageal fistula organoids in the laboratory by inducing the trachea and esophagus simultaneously in a foregut organoid, the report stated.