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Leecarlo ML. Gaol
Division of Pediatric Surgery, Department of Surgery, Tarakan General Hospital, Jakarta, Indonesia; Faculty of Medicine, Universitas Kristen Krida Wacana, Jakarta, Indonesia

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Hypoxia-conditioned mesenchymal stem cell secretome for anal sphincter injury: A preclinical study of tissue repair and regenerative outcomes Leecarlo ML. Gaol; Bryan A. Wijaya; Yohanes Firmansyah; Fiona V. Setiawan; Yuliana SK. Prabaningrum
Narra J Vol. 6 No. 3 (2026): December 2026 (In Press)
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v6i3.3142

Abstract

Fecal incontinence may arise following anal sphincter injury, yet currently available treatments have limited capacity to restore sphincter integrity. The secretome derived from hypoxia-conditioned mesenchymal stem cells (MSCs) represents a potential cell-free regenerative therapy because of its putative immunomodulatory and tissue-remodeling properties. The aim of this study was to investigate the effects of hypoxia-conditioned human umbilical cord MSC secretome on inflammation, fibrosis, collagen deposition, and hypoxia-inducible factor-1 alpha gene (HIF-1A) expression following sphincterotomy. Male Sprague–Dawley rats were randomly assigned to receive either hypoxia-conditioned MSC secretome or 0.9% NaCl after surgical sphincterotomy. Histopathological evaluations using hematoxylin and eosin and Masson’s trichrome staining were conducted at 24 hours and 42 days, and HIF-1A was assessed using quantitative real-time polymerase chain reaction (qRT-PCR). At day 42, inflammation scores were numerically lower in the secretome group than in the control group, although the between-group difference was not statistically significant (0.00±0.00 vs 0.25±0.25; p=0.317). Fibrosis scores showed a similar numerical pattern without a significant difference (3.25±0.25 vs 3.50±0.29; p=0.495). Conversely, the secretome group exhibited numerically greater collagen area (79.93±11.11×10⁴ µm² vs 59.25±7.44×10⁴ µm²; p=0.149) and percentage collagen area (68.81±4.48% vs 56.07±3.29%; p=0.083), but neither difference reached statistical significance. HIF-1A expression was also numerically higher in the secretome group at day 42, without a statistically significant between-group difference (27.47±0.38 vs 26.44±0.54; p=0.149). Although the secretome group exhibited numerically lower inflammation and fibrosis scores and greater collagen deposition and HIF-1A expression, these differences were not statistically significant. Further adequately powered studies incorporating functional, histological, and molecular endpoints are required to clarify the regenerative potential of hypoxia-conditioned MSC secretome in anal sphincter injury.