Cellular "glue" to regenerate tissue, heal wounds, regrow nerves

Cellular “glue” to regenerate tissue, heal wounds, regrow nerves

Researchers at UC San Francisco (UCSF) have developed molecules that act like “cell glue”, allowing them to precisely direct how cells bind to each other. This discovery represents a major step towards the construction of tissues and organs, a goal long sought after by regenerative medicine.

Adhesive molecules are found naturally throughout the body, holding its tens of trillions of cells together in highly organized patterns. They form structures, create neural circuits and guide immune cells to their targets. Membership also facilitates communication between cells for the body to function as a self-regulating whole.

in a new studypublished in the December 12, 2022 issue of Naturethe researchers engineered cells containing personalized adhesion molecules that bound to specific partner cells in predictable ways to form complex multicellular assemblies.

“We were able to engineer cells in a way that allows us to control which cells they interact with, as well as the nature of that interaction,” said lead author Wendell Lim, Ph.D., professor emeritus Byers of Cellular and Molecular Pharmacology and director of the Cell Design Institute at UCSF. “It opens the door to building new structures like tissues and organs.”

Regenerate connections between cells

Body tissues and organs begin to form in utero and continue to develop during childhood. By adulthood, many of the molecular instructions that guide these generative processes have disappeared and some tissues, such as nerves, cannot heal from injury or disease.

Lim hopes to overcome this by engineering adult cells to make new connections. But this requires an ability to precisely engineer how cells interact with each other.

“The properties of a tissue, like your skin for example, are determined in large part by how the different cells are organized in it,” said Adam Stevens, Ph.D., Hartz Fellow at the Cell Design Institute and first author . paper. “We are designing ways to control this organization of cells, which is essential for being able to synthesize tissues with the properties we want them to have.”

Much of what makes any given tissue distinct is how its cells relate to each other. In a solid organ, like a lung or a liver, many cells will be tied together quite tightly. But in the immune system, weaker bonds allow cells to travel through blood vessels or crawl between tightly bound cells in the skin or body tissues to reach a pathogen or wound.

To direct this quality of cell bonding, the researchers designed their two-part adhesion molecules. Part of the molecule acts as a receptor outside the cell and determines which other cells it will interact with. A second part, inside the cell, regulates the strength of the bond that is formed. The two parts can be mixed and matched in a modular way, creating a network of custom cells that bond in different ways across the spectrum of cell types.

The code behind cell assembly

Stevens said these findings have other applications as well. For example, researchers could design tissues to model disease states, to facilitate their study in human tissues.

Cell adhesion has been a key development in the evolution of animals and other multicellular organisms, and custom adhesion molecules may offer a deeper understanding of how the path from single organisms to multicellular organisms began.

“It’s very exciting that we now understand so much more about how evolution may have started building bodies,” he said. “Our work reveals a flexible molecular adhesion code that determines which cells will interact and how. Now that we are beginning to understand it, we can harness this code to direct how cells come together in tissues and structures. organs. These tools could be really transformative.”

Authors: Other authors include Josiah Gerdts, Ki Kim and Wesley McKeithan from the UCSF Cell Design Institute and the Department of Cellular and Molecular Pharmacology, Jonathan Ramirez and Faranak Fattahi from the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research and the Dept. of Cellular and Molecular Pharmacology, Coralie Tentesaux and Ophir Klein of the UCSF Craniofacial Biology Program and Department of Orofacial Sciences, and Andrew Harris and Dan Fletcher of the UC Berkeley Department of Bioengineering.

Funding: This work was supported by NSF grant DBI-1548297, NIH grant U01CA265697, and a postdoctoral fellowship from the Damon Runyon Cancer Research Foundation (DRG-#2355-19).

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