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New way to generate human cartilage

Researchers at the University of Montana and their partners have found a new method to generate human head and neck cartilage.

Mark Grimes, a professor of biology in the U-M Division of Biological Sciences, said they have induced the stem cells to become the type of cell that normally forms human craniofacial cartilage. Stem cells can replicate and also become different types of cells.

“The cells that normally give rise to this type of cartilage are called neural crest cells,” Grimes said. “We found a novel method to generate craniofacial organoids from neural crest cells.”

Organoids are a simplified, miniature version of an organ that mimics the architecture and genetic expression of the organ. “Organoids are a good model for certain human tissues that we can study in ways that are not possible using human tissue,” he said.

Grimes said there is a critical unmet need for new methods to regenerate human cartilage for the 230,000 children born annually in the U.S. with craniofacial defects. Growing cartilage in the lab could also lead to effective treatments to repair craniofacial cartilage damage due to injury.

The researchers studied gene expression data at the RNA and protein level to reveal how cartilage cells arise from stem cells. They revealed that stem cells communicate in the early stages to become elastic cartilage, which forms human ears.

To achieve this, the team used extensive biomarker analysis and machine learning pattern recognition techniques to understand the cell signaling pathways involved when cells differentiate into cartilage.

It is difficult to reconstruct natural features such as a person’s ears, nose or voice box with current plastic surgery techniques, and transplanted tissue is often rejected without immunosuppressants.

“To use patient-derived stem cells to generate craniofacial cartilage in the laboratory, it is necessary to understand differentiation mechanisms specific to humans,” Grimes said. “Our goal is to develop a protocol for the generation of craniofacial cartilage for transplantation using human stem cells.”

The research was published in the journal. iScience. In addition to Grimes, UM contributing authors include Lauren Foltz, Nagashree Avabhrath, and Jean-Marc Lanchy. Other authors are Bradly Peterson of Missoula’s Pathology Consultants of Western Montana and Tyler Levy, Anthony Possemato and Majd Ariss of Cell Signaling Technology of Danvers, Massachusetts.