In News:

A team of Indian scientists may have found a way to improve the drainage capacity of lymphatic vessels in the liver and intestine that fails in case of cirrhosis, by using nanocarriers filled with a powerful protein called VEGF-C.

Understanding Liver Cirrhosis

Cirrhosis is the advanced stage of chronic liver disease where healthy tissue is replaced by scar tissue due to prolonged inflammation. This structural distortion affects both blood and lymphatic vessels in the liver and intestine, impairing circulation and fluid balance.

Causes:

• Excessive alcohol consumption
• NASH (Non-Alcoholic Steato-Hepatitis)
• Chronic viral infections such as Hepatitis B and C

Symptoms (often in advanced stages): extreme fatigue, loss of appetite, easy bruising or bleeding, swelling in legs/ankles (edema), and abdominal fluid accumulation (ascites).

The Problem of Lymphatic Dysfunction

In cirrhosis, lymphatic vessels (mesenteric lymphatic vessels or mLVs) become dilated and dysfunctional. Normally, these vessels drain interstitial fluid, proteins, and immune cells back into venous blood.

• In cirrhosis, lymph production increases nearly 30-fold due to portal hypertension and liver congestion.
• Dysfunctional lymph flow leads to ascites (abdominal fluid buildup), one of the most serious complications of decompensated cirrhosis.
• Currently, there is no effective therapy to correct this lymphatic dysfunction.

The VEGF-C Based Breakthrough

A joint team from the Institute of Liver and Biliary Sciences (ILBS), New Delhi and the National Institute of Pharmaceutical Education and Research (NIPER), Guwahati has developed a novel therapy using Vascular Endothelial Growth Factor-C (VEGF-C).

• Role of VEGF-C: A key pro-lymphangiogenic factor that binds to VEGFR-3 receptors, stimulating the growth of new lymphatic vessels and enhancing drainage.
• Challenge: VEGF-C has a short half-life, is hydrophilic, and can cause systemic side effects.

The Innovation: Nanocarriers

• Scientists at NIPER designed reverse micelle-based nanocarriers to encapsulate VEGF-C, ensuring targeted delivery to gut lymphatic vessels.
• These nanocarriers specifically bind to VEGFR-3 homodimers, maximizing efficacy and minimizing side effects.
• The formulation was delivered orally in animal models, ensuring uptake by intestinal lymphatic vessels.

Findings (Animal Studies)

• Significant increase in mesenteric lymph drainage
• Reduction in ascites and portal hypertension
• Enhanced cytotoxic T-cell immunity in lymph nodes
• Reduction in local and systemic bacterial load

Significance and Future Prospects

• This is the first study to demonstrate that therapeutic lymphangiogenesis using VEGF-C can reconstruct fragmented lymphatic networks and restore function in advanced cirrhosis.
• Funded by the DST Nano Mission and published in JHEP Reports, it marks a major step in translational medicine.
• Next steps: Preclinical studies in larger animals, followed by human clinical trials to establish safety, dosage, and efficacy.