Cellular “glue” to Regenerate Tissues, Heal Wounds, Regenerate Nerves

Cell regeneration concept illustration

Researchers have developed molecules that act like “cell glue,” allowing them to control exactly how cells stick together. This represents a significant advance towards tissue and organ building, which has been a key goal in the field of regenerative medicine for a long time.

Synthetic molecules that attach to cells could boost regenerative medicine

Scientists at the University of California, San Francisco (UCSF) have engineered molecules that act like “cell glue,” allowing them to precisely direct how cells stick together. The discovery represents a major step toward building tissues and organs, a long-sought goal of regenerative medicine.

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

In a new study, published in the December 12, 2022, issue of Naturethe researchers engineered cells containing personalized adhesion molecules that bind with 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 and also control the nature of that interaction,” said senior author Wendell Lim, PhD, Byers Distinguished Professor of Cellular and Molecular Pharmacology and director of the Institute for Cell Design. from UCSF. “This opens the door to building novel structures like tissues and organs.”

wendell lim

Wendell Lim, PhD, director of the UCSF Cell Design Institute, holds up a cell model in his office on the UCSF Mission Bay Campus. Credit: Elena Zhukova

Regenerating Connections Between Cells

Body tissues and organs begin to form in the womb and continue to develop throughout 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 doing this requires the ability to precisely design how cells interact with each other.

“The properties of a tissue, like skin, for example, are largely determined by how the different cells within it are organized,” said Adam Stevens, PhD, a Hartz Fellow at the Cell Design Institute and first author of the paper. . “We are devising ways to control this organization of cells, which is essential to be able to synthesize tissues with the properties that we want them to have.”

Much of what distinguishes a given tissue is how tightly its cells are held together. In a solid organ, such as a lung or liver, many of the cells will be held together quite tightly. But in the immune system, weaker links allow cells to flow through blood vessels or crawl between tightly packed cells in skin or organ tissue to reach a pathogen or wound.

“We are devising ways to control this organization of cells, which is essential to be able to synthesize tissues with the properties that we want them to have.” — Adams Stevens, PhD

To drive that quality of cell attachment, the researchers designed their adhesion molecules in two parts. One part of the molecule acts as a receptor on the outside of the cell and determines which other cells it will interact with. A second part, inside the cell, tunes the strength of the bond that is formed. The two parts can be mixed and matched in a modular fashion, creating an array of custom cells that come together in different ways across the spectrum of cell types.

The underlying cell assembly code

Stevens said these discoveries have other applications as well. For example, researchers could engineer tissues to model disease states, making it easier to study them in human tissue.

Cell adhesion was a key development in the evolution of animals and other multicellular organisms, and personalized adhesion molecules may offer a deeper understanding of how the journey from single to multicellular organisms began.

“It’s very exciting that we now understand much more about how evolution may have started to build bodies,” he said. “Our work reveals a flexible molecular adhesion code that determines which cells will interact and in what way. Now that we’re beginning to understand it, we can harness this code to direct how cells assemble into tissues and organs. These tools could be truly transformative.”

Reference: “Programming of Multicellular Assembly with Synthetic Cell Adhesion Molecules” by Adam J. Stevens, Andrew R. Harris, Josiah Gerdts, Ki H. Kim, Coralie Trentesaux, Jonathan T. Ramirez, Wesley L. McKeithan, Faranak Fattahi, Ophir D. Klein, Daniel A. Fletcher, and Wendell A. Lim, December 12, 2022, Nature.
DOI: 10.1038/s41586-022-05622-z

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

Money: 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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