Influencing stem cell behaviour with nanomaterials
Prof. dr. Sabine van Rijt (MERLN) investigates how we can influence stem cell behaviour using nanomaterials. Through her chair in ‘Inorganic Nanomaterials for Regenerative Medicine’, she is developing a toolbox to identify the materials, structures and signals that can best facilitate the repair of damaged tissue. Van Rijt: “I want to understand which signals contribute most effectively to stem cell behaviour. It is fundamental research and we take a very broad approach. I think that is important. Ultimately, our knowledge will have relevance and impact across many research fields”.
Two elements are always present in Sabine van Rijt’s research: stem cells and nanoparticles. The overarching idea is to use these nanoparticles to influence stem cell behaviour. Van Rijt: “Stem cells form the basis of regenerative medicine. They have exactly the properties needed for tissue repair: they can self-renew, proliferate and differentiate, and also possess anti-inflammatory qualities. Imagine you break a bone. Stem cells receive a signal that there is a fracture and migrate to the site of the injury. There, they start to multiply and repair the bone. In our research, we try to stimulate that process by adding nanoparticles to stem cells. These are extremely small particles, precisely within the biological size range that allows them to interact with cells. They are small enough to be taken up by a cell, yet large enough to carry something, a biomolecule such as DNA, a protein or a drug, that can help in tissue regeneration”.
Guiding stem cells
Her inaugural lecture was entitled The environments that shape us: guiding cells through interaction. Van Rijt: “In my research, I use different ways of guiding stem cells; like a toolbox. This includes creating structures in which stem cells feel comfortable, using nanoparticles to deliver specific messages to stem cells, and tracking stem cells in the body to see whether they reach the right location and do what we want them to do”.
Creating synthetic structures
Van Rijt: “Stem cells are extremely important for repairing damaged tissue, but when you simply inject them, they often do not survive. They do not want to just float around; they need a structure. In the body, cells are also embedded in a structure: a tissue or extracellular matrix. Imagine that a large piece of bone is missing, too large for the stem cells to repair on their own. In that case, we want to be able to place a structure at the site of the fracture. If the stem cells feel comfortable in the matrix and start to multiply, they will eventually create their own matrices and repair the bone. To achieve this, we recreate these kinds of structures. We try to determine exactly what needs to be incorporated into the structure to make stem cells ‘stick’. This is a complex process because different components are important, and these can vary depending on the type of tissue: the material, the strength of the structure and how it responds to pressure. For bone tissue, for example, a different stiffness is required than for liver tissue. Much of the work in the field of biomaterials focuses on creating these kinds of synthetic structures. If we succeed, we will be less dependent on donor tissue, which is beneficial due to reduced risk of rejection and better availability”.
We also examine whether the stem cells actually perform the specific task we have in mind. I call this ‘listening to stem cells.
Providing signals
Van Rijt: “In the early days of the field, people still assumed that a replicated matrix was enough and that the cells would do everything themselves. We now know that more is needed and that you can also guide the stem cell. Sticking to the matrix is an important first step, but ultimately we want stem cells to differentiate and perform a specific task. In our work, when we are creating a synthetic matrix using polymers, or hydrogels, we also add nanoparticles that can deliver a certain bioactivity, a signal to the stem cells. For this, we only need to look at the biological system; the body naturally provides signals that stem cells respond to, such as in the example I mentioned of a bone fracture. We can incorporate those same signals into nanoparticles to enhance that action. We therefore study closely which signals the body naturally uses to communicate with stem cells and which are most important.
Alongside identifying which signals stem cells need, we also investigate how we can deliver them in the best way. We work with all kinds of materials, such as proteins and ions, but also growth factors and genetic material. Blood vessel regeneration is an important signal to deliver. Often it is even the first signal needed, acting as a kind of catalyst. After all, most tissues have blood vessels to supply them with nutrients. If you stimulate bone growth without integrating blood vessels, you will not end up with fully functional bone. The question we always ask is: what is the minimum needed for regeneration? We don’t need to provide all the signals, just those that will kickstart the regenerative process”.
Tracing
Van Rijt: “Besides giving stem cells signals to perform specific tasks, we also examine whether they actually perform the specific task we have in mind. I call this ‘listening to stem cells’. To do this, we give the nanoparticles a label that allows us to follow, or trace, them in the body. It is also possible to load the nanoparticles with drugs, called theranostics, allowing us to see whether a drug is delivered to the right location and what happens afterwards, including how effective it is”.
Impact
Van Rijt: “Ultimately, this research could have an impact in many areas. I often use bone tissue as an example because we do a lot of research in this area, but ultimately our materials could be applicable to all organs. Because I have a background in fundamental research, I find it fascinating to understand which signals best contribute to stem cell behaviour. It’s like discovering a set of rules as: ‘if you add this to your material, you get this response from the stem cell’. Generating more knowledge so that we can develop better materials that can ultimately be used to help people. The idea is that, if a part of an organ is missing, you can inject a synthetic material at that site which remains there, initiates the entire regenerative process and then disappears again at the right moment. That, essentially, is the whole idea behind the field of biomaterials.”
Text: Eline Dekker
Photo: Joey Roberts