For decades, medical researchers have been searching for ways to prevent organ transplant rejection. Current treatments focus on suppressing T cells, part of the adaptive immune system. However, this approach has its limitations. A new study from Mass General Brigham sheds light on a previously untapped area: the innate immune system. Researchers identified a natural “brake” within this system – the inhibitory receptor Siglec-E (SigE) and its human counterparts, Siglec-7 and Siglec-9. This receptor plays a crucial role in preventing overactivation of immune cells that drive rejection.

When this brake is missing or malfunctioning, inflammation worsens, leading to faster rejection in preclinical models. Importantly, transplant patients with higher levels of Siglec-7 and Siglec-9 showed better graft survival, highlighting this pathway as a promising target for new therapies. Results were published in Science Translational Medicine.

“For decades, we’ve focused almost exclusively on controlling T cells to prevent rejection,” said Leonardo Riella, MD, PhD, medical director of Kidney Transplantation at Massachusetts General Hospital (MGH). “Our research shows that the innate immune system plays a pivotal role. By harnessing natural inhibitory pathways like Siglec-E, we can develop safer, more precise therapies that protect transplanted organs without compromising overall immune health.”

To conduct their studies, the researchers used mouse models of heart, kidney, and skin transplantation to study the roles of SigE. They found that recipients deficient in SigE had accelerated acute rejection and increased inflammation. The researchers also looked at the levels of the receptors in samples from human transplant biopsies, finding that higher levels of the receptors were associated with improved allograft survival.

“This discovery paves the way for next-generation treatments that address both arms of the immune system, offering hope for longer-lasting transplant success and reducing the need for lifelong immunosuppression,” said Riella.

Revolutionizing Skin Research with Artificial Hydrogels

The human skin is the largest organ, accounting for about 15% of our body weight. It plays a vital role in protecting us from pathogens, dehydration, and temperature extremes. However, skin diseases such as skin cancer, chronic wounds, and autoimmune skin diseases are widespread, yet often poorly understood.

To address this knowledge gap, researchers at Empa have been working on developing an artificial model of human skin. This living “artificial skin” will enable scientists to simulate skin diseases, ultimately leading to a better understanding of their causes and treatment options. Unlike computer or plastic models, this innovative approach involves creating a model that contains cells and emulates the layered and wrinkled structure of human skin.

To recreate such complexity, researchers require suitable building materials. Recently, Empa scientists have made significant progress in developing hydrogels that meet these complex requirements while being easy to manufacture. The basis of their success lies in gelatin derived from the skin of cold-water fish.

Hydrogels: A Suitable Substitute for Skin Extracellular Matrix

Like most tissues, human skin consists of cells embedded in a network of proteins and other biomolecules called extracellular matrix. This matrix provides the tissue with shape and structure while sustaining the cells. However, it differs from one tissue to another – even within different layers of the skin.

Researchers have discovered that hydrogels can simulate this complex extracellular matrix. These special polymers absorb large quantities of water and other fluids, making them ideal for recreating the skin’s extracellular matrix. Moreover, many hydrogels can be processed using a 3D printer, allowing researchers to combine multiple materials and cell types into a single structure – just like real skin.

The Empa team has developed a fish gelatin-based hydrogel that can be cross-linked in just a few steps. This non-swelling hydrogel can be printed with skin cells, enabling the creation of a 3D-printed artificial skin model that closely resembles human skin.

A Promising Tool for Wound Healing

The researchers’ innovative hydrogel has far-reaching implications. Without the addition of living cells, it can be used as a dressing material. This biologically compatible material is safer and carries a lower risk of disease transmission compared to materials based on mammalian gelatin.

Moreover, the fish skin from which this hydrogel is derived is being researched as a promising tool for wound healing. The Empa team’s hydrogel is more homogeneous and can be tailored precisely to meet patient needs – with different shapes, thicknesses, and firmness levels.

The researchers have applied for a patent for their fish gelatin-based hydrogel and plan to finish developing the living skin model. This will make it available to other scientists, promoting a better understanding of skin disease development and treatment options.

Chronic rhinosinusitis, a condition characterized by inflammation of the nasal and sinus cavities, affects millions of people worldwide. Symptoms include nasal congestion, mucus secretion, and pressure in the sinuses. In severe cases, the disease can be associated with asthma or NSAID-exacerbated respiratory disease (N-ERD). The standard treatment involves nasally administered corticosteroids, which can be supplemented with orally administered corticosteroids for the polypoid form of the disease.

For patients who do not respond to medical treatments, endoscopic sinus surgery is often considered. However, a significant number of patients may require revision surgery due to persistent symptoms and disease progression. In fact, research suggests that up to 28% of patients undergoing endoscopic sinus surgery for chronic rhinosinusitis may need revision surgery within one year.

A new study published in Clinical and Translational Allergy has introduced a novel CT-scan based risk score to predict the likelihood of revision endoscopic sinus surgery. The Sinonasal Radiological Score (SR score) takes into account indicators such as non-detectable anatomy of the nasal turbinates, which is often associated with polypoid mucosal swelling, and obstructed drainage of the frontal sinus.

In comparison to the existing Lund-Mackay scoring system, the SR score provides a more accurate assessment of the risk of revision surgery. The study analyzed data from 483 patients with chronic rhinosinusitis, including those who underwent endoscopic sinus surgery within one year following their CT scan. Results showed that conditions such as asthma and N-ERD increased the risk of revision surgery.

This breakthrough research highlights the importance of early prediction of disease progression and planning for further treatment. By using the new SR score in conjunction with conventional medical and surgical treatments, clinicians can identify patients at risk of revision surgery and tailor their treatment approach accordingly.