Repairing or replacing any organ or tissue of the human body, to compensate for a deficiency, such is the challenge of regenerative medicine. Recently, researchers have developed molecules that act as cellular “glue”, allowing them to precisely direct how cells bind to each other. This advance is a major step in achieving a long-coveted goal, the generation (or regeneration) of tissues and organs.
Our body is made up of trillions of cells, organized in complex patterns to perform all of its functions. Cell adhesion molecules are therefore essential and ubiquitous in multicellular organisms to maintain all these assemblies in a stable and solid manner.
The latter specify precise cell-cell interactions in processes as diverse as tissue development, the guidance of immune cells to their target and the wiring of the the nervous system. Membership also facilitates communication between cells for the body to function as a self-regulating whole.
The current issue of regenerative medicine is to generate new organs when they are too old or deficient, by reprogramming differentiated adult cells to make them pluripotent A pluripotent cell is a stem cell capable of spawning any type of specialized cell once more. This is the next chapter of the transplantation organs, but using stem cells instead of donor organs, the supply of which is limited.
In addition, body tissues and organs begin to form in utero and continue to develop during childhood. In adulthood, many molecular instructions that guide these generative processes disappear and some tissues, such as nerves, cannot heal from injury or disease.
In this context, researchers at UC San Francisco (UCSF) have designed personalized adhesion molecules that act as a “cellular glue”, allowing them to precisely and predictably direct the bonds between cells to form assemblies. complex multicellular structures, such as human body tissues or organs. The study is published in the journal Nature.
A toolbox to restore cell-to-cell interactions
You should know that what distinguishes one tissue from another is the way its cells are linked to each other. In a solid organ, like the lungs, the many cells are tied together quite tightly. But in the immune system, weaker bonds allow cells to move through blood vessels or crawl between tightly bound cells in the skin, for example, to reach a pathogen or a wound.
Wendell Lim, PhD, director of UCSF’s Cell Design Institute and co-author, explains that there’s a need to precisely design how cells interact with each other.
To understand this cell binding and direct it for regenerative medicine purposes, the researchers designed synthetic cell adhesion molecules (synCAM) in two parts. Part of the molecule acts as a receptor outside the cell and determines which other cells it interacts with. A second part is made up of the intracellular domains of native adhesion molecules, such as cadherins and integrins, making it possible to regulate the strength of the bond that is formed.
The resulting molecules produce personalized cell-cell interactions with adhesion properties similar to the interactions found live. 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.
This “toolbox” of adhesion molecules allows the rationally programmed assembly of new multicellular architectures, as well as the remodeling of damaged tissues in the body.
Adam Stevens, PhD, Hartz fellow at the Cell Design Institute and first author of the study, says in a communiqué : « We are designing ways to control this organization of cells, which is essential to be able to synthesize tissues with the properties we want them to have. ».
In addition to replacing a damaged or dysfunctional organ, tissue livethis discovery might allow, according to the authors, to design tissues to model pathological states, in order to facilitate their study in human tissues.
Cellular assemblies encoded throughout evolution
As the researchers recall, cell adhesion was a key development in the evolution of animals and other multicellular organisms. In fact, personalized adhesion molecules may offer a new avenue for deeper understanding of how single-celled organisms began to evolve into multicellular organisms, the precursors of current species.
Adam Stevens concludes: It’s very exciting that we now understand a lot more regarding how evolution may have started building bodies. “. He adds : ” 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 assemble into tissues and organs. These tools might be truly transformative ».
