WOFAPS 2025 8th World Congress of Pediatric Surgery

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Oral Presentation - 84

EMERGING THERAPIES for PEDIATRIC LIVER DISEASES: FOCUS on the ANTIFIBROTIC and ANGIOGENIC EFFECTS of hUC-MSC SECRETOME

Eko Purnomo 1, Silvia Apriliana 1, Febriofca G Yatalaththof 1, Dwi AA Nugrahaningsih 2, . Gunadi 3
1 Pediatric Surgery Division, Departement of Surgery, Faculty of Medicine, Public Health and Nursing/Academic Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia
2 Pharmacology and Therapy Department, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada
3 Pediatric Surgery Division, Department of Surgery/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr.Sardjito Hospital

Background

Biliary atresia is a rare neonatal hepatobiliary disorder with progressive inflammation and obstructive fibrosing cholangiopathy, leading to neonatal jaundice and bile flow obstruction. Despite interventions such as Kasai portoenterostomy and liver transplantation, significant challenges remain, necessitating the exploration of adjunctive therapies. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) secretome presents a promising avenue for mitigating liver fibrosis.

Aims

This study aims to elucidate the antifibrotic mechanisms of the hUC-MSC secretome in biliary atresia and explores its potential role in promoting angiogenesis for liver regeneration.

Methods

Thirty 3-week-old Sprague-Dawley rats were divided into experimental (n=24) and control (n=6) groups, undergoing bile duct ligation. Post-ligation, rats received varying volumes of Hyp-UCMSC secretome or control treatment intravenously on days 15 and 16 post-surgery. Rats were euthanized 29 days post-operation for blood and tissue collection. Blood samples were analyzed for AST, ALT, and total bilirubin levels. Liver tissues were subjected to histological examination and qPCR for TGF-β, α-SMA, VEGF, and HIF-1α gene expression.

Results

AST, ALT, and total bilirubin levels significantly increased in the BDL group 28 days post-surgery compared to the sham group (p < 0.05). Treatment with 400 µL Hyp-UCMSC secretome resulted in lower fibrosis, biochemical liver and bilirubin levels compared to the BDL group (p < 0.05). Additionally, the treatment inhibited the expression of TGF-β, α-SMA, VEGF, and HIF-1α mRNA levels, normalized to GAPDH expression, highlighting the potential role of Hyp-UCMSC secretome in reducing fibrosis and promoting angiogenesis in liver regeneration.

Conclusion

The findings highlight the therapeutic potential of Hyp-UCMSC secretome in mitigating liver fibrosis and improving biochemical liver parameters in a biliary atresia model. Hyp-UCMSC secretome could be a promising adjunctive therapy for biliary atresia, offering a novel approach to managing this challenging condition and paving the way for future clinical applications.

Keywords: Biliary Atresia, Liver Failure, Secretome, Regeneration, Therapy

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