Transforming Lives with PPCN: A New Era in Islet Transplantation for Chronic Pancreatitis

 

Chronic pancreatitis (CP) is a severe condition caused by chronic inflammation of pancreatic tissue. As the inflammation progresses, pancreatic tissue is damaged, resulting in a large loss of insulin-producing beta cells, and many patients acquire diabetes. CP management is a difficult and comprehensive process. It usually includes lifestyle changes, pain management, and nutritional support. When these efforts prove insufficient, surgical intervention may be required. One such surgical treatment is complete pancreatectomy (TP), which is followed by intrahepatic islet autologous transplantation (IAT), also called as TP-IAT. This method involves transplanting the patient's own insulin-producing islet cells into the liver to assist manage blood sugar levels. This procedure accidentally destroys 50-80% of the islets, and one-third of patients develop diabetes as a result of the surgery. 70% of patients require insulin shots three years after surgery, which have a number of adverse effects such as weight gain, hypoglycemia, and fatigue.

Given the existing limitations of the TP-IAT strategy, there is an urgent need for improved islet transplantation techniques as well as alternate transplant locations that can provide a supportive environment for islet survival and function. The omentum, a highly vascularized layer of fat within the abdomen, is one intriguing area of inquiry. The omentum has various benefits, including easy access and the possibility of localised islet engraftment.

PPCN as a Novel Hydrogel for Islet Transplantation

Researchers are looking into using a new hydrogel called Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN). PPCN is a water-soluble, degradable macromolecule that converts from liquid to gel at body temperature. This feature allows it to easily entrap and carry islets to the omentum, where it gels and creates a supportive environment for the islets.

What makes PPCN so effective? First, its antioxidant and anti-inflammatory characteristics provide a protective bubble around the transplanted islets, preventing them from the oxidative damage that is common in CP. PPCN also features a unique temperature-responsive phase-changing capability. When it comes into touch with bodily tissue, it solidifies into a hydrogel, enclosing the islets without the need for additional adhesives. This not only simplifies the transplanting process, but also ensures that the islets remain in place and receive the necessary blood supply.

 

Figure. A schematic showing PPCN-mediated islet protection against oxidative stress to maintain islet function during omentum transplantation.

Furthermore, PPCN is biocompatible and resorbable, which means it integrates into the body and reduces the danger of persistent inflammation or fibrosis. This quality ensures that the transplanted islets have a supportive environment to thrive in the long term.

Initial research in nonhuman primates has revealed that PPCN can sustain islet transplantation in the omentum for more than 100 days, resulting in vascularized islets with little exogenous insulin needs. In conclusion, the creation of PPCN represents a huge step forward in the attempt to enhance islet transplantation results for patients with CP. By creating a supportive microenvironment that promotes islet survival and function, PPCN has the potential to lower the incidence of post-transplant diabetes and improve the quality of life for patients.

 

REFERENCES :

1. Burke, Jacqueline A., Yunxiao Zhu, Xiaomin Zhang, Peter D. Rios, Ira Joshi, Daisy Lopez, Hafsa Nasir et al. "Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum." Science Advances 10, no. 23 (2024): eadk3081. DOI: 10.1126/sciadv.adk3081

IMAGE SOURCE : 

1. Cover image : https://www.nature.com/articles/s41574-019-0296-1 

2. Science Advances : https://www.science.org/doi/full/10.1126/sciadv.adk3081