Exploring regeneration in the spiny mouse – PhD Defense Henriette van Beijnum

Most mammals cannot fully repair wounds. Also in humans, wound healing often results in scarring and loss of function, particularly in vital organs such as the heart after a heart attack. The spiny mouse is different: It can fully repair its skin and other complex tissues without scarring. This phenomenon is called regeneration. “The spiny mouse is a fascinating model to study regeneration,” Van Beijnum explains. “By examining the unique characteristics of this animal, we will gain a better understanding of the possibilities for developing therapies to improve wound healing in humans and increase the likelihood of full recovery.”

Wound healing in the spiny mouse

Van Beijnum’s research focused on unraveling the processes behind regeneration in the spiny mouse. She used advanced techniques to assess which genes are active in different parts of a wound in the skin. She found important differences between the spiny mouse and non-regenerative species such as the common house mouse and gerbil. “We saw differences in the immune response, which made us suspect that the porcupine mouse’s ability to regenerate is related to specific properties of the immune system,” Van Beijnum said. Another striking discovery was that the ear of the spiny mouse did not uniformly all at once. In fact, the wound healed from the side closer to the head, working slowly toward the tip of the ear. This shows that cells or factors closer to the head may play a role in regeneration.

The heart can heal, too

Van Beijnum did not restrict her research to skin wounds alone. She also investigated whether the unique properties of the spiny mouse are applicable to heart tissue, which is important because of the global impact of cardiovascular disease. In humans and most mammals, a heart attack causes irreversible damage and scarring, which reduces the heart’s ability to pump blood. Van Beijnum saw that in spiny mice, heart functions recover much better after a heart attack than in the common house mouse. Spiny mice produce more new blood vessels and immature heart muscle cells, with scarring that is better organized. These factors enhance the likelihood of recovery following a heart attack. “Our findings challenge the traditional notion that scarring is inevitable after a heart attack,” Van Beijnum emphasizes. “The spiny mouse shows that it is possible to preserve tissue function even after severe damage.

The role of the extracellular matrix

A crucial component of tissue repair proves to be the extracellular matrix, a network of proteins that provides structural support to tissues. Van Beijnum discovered that the extracellular matrix of spiny mice is much more flexible than in other animals. Their scar tissue forms a flexible “basket-weave” pattern, quite different from the rigid, aligned fibers that are seen in other animals. This flexibility makes the heart tissue of the spiny mouse functional even after injury. “Discovering the “basket-weave” pattern was a real breakthrough,” Van Beijnum says. “It shows that scars don’t always have to be stiff and unusable. If replicated in humans, this discovery could revolutionize the treatment of heart attacks and chronic wounds.”

From mice to medicine

The findings of Van Beijnum’s research hold promise for the medical field. By identifying the factors involved in regeneration in spiny mice, her work lays the groundwork for new therapies. This could involve the development of drugs or biomaterials to enhance repair processes. This could be important for patients with heart disease, skin burns or chronic wounds. However, Van Beijnum emphasizes that more research is required before this knowledge can be applied to humans. “Further research and clinical validation are needed to turn these discoveries into safe and effective treatments for humans,” she says. “But the insights that we have gained are a crucial first step.”

Celebrate small victories in research

Looking back on her PhD journey, Van Beijnum expresses her gratitude for the support of her colleagues and the inspiring collaboration within her research groups. “The absolute highlight of my PhD was working with colleagues who shared the same passion for research,” she says. “Coming up with ideas and solving problems together made the challenges not only manageable, but also exciting.” She also reflects on the challenges of the PhD process, including experiments that did not always yield the desired results. Her advice to current and future PhD students: “Focus on your strengths and celebrate small victories. Also ensure a healthy work-life balance. Take time for friends and hobbies and avoid spending all your time in the lab. That balance is essential for staying motivated.”