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Biomedicines
Volume 14
Issue 3
10.3390/biomedicines14030657
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Article

Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation

by
Basri Satılmış
1,*,
Egemen Çiçek
1,2,
Serdar Karakaş
1,2,
Koray Kutlutürk
1,2,
Elif Kayhan
3,
Mehmet Gül
4,
Emrah Otan
1,2,
Tevfik Tolga Şahin
1,2 and
Sezai Yılmaz
1,2
1
Liver Transplant Institute, İnönü University, 44280 Malatya, Turkey
2
Department of Surgery, Faculty of Medicine, İnönü University, 44280 Malatya, Turkey
3
Department of Histology and Embryology, Faculty of Medicine, Malatya Turgut Özal University, 44900 Malatya, Turkey
4
Department of Histology and Embryology, Faculty of Medicine, İnönü University, 44280 Malatya, Turkey
*
Author to whom correspondence should be addressed.
Biomedicines 2026, 14(3), 657; https://doi.org/10.3390/biomedicines14030657
Submission received: 10 January 2026 / Revised: 22 February 2026 / Accepted: 11 March 2026 / Published: 13 March 2026
(This article belongs to the Special Issue Advanced Research into Adipose‐Derived Stem Cells)
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Abstract

Background/Objectives: Bile duct ligation (BDL), characterized by marked inflammation and fibrosis, effectively mimics many clinical conditions and is a valuable tool for investigating biliary regeneration. Our objective was to clarify the therapeutic benefits of adipose-derived stem cell (ADSC) treatment and signaling pathways mediating regenerative processes in a rat model of BDL. Methods: The BDL model was performed on Sprague–Dawley rats, and ADSC was administered intrasplenically at a dose of 106 cells per animal. Liver function tests, gene and protein expression analyses, histological evaluation, and immunohistochemistry staining were performed to assess liver function, signaling pathways, inflammation, and fibrosis. Results: ADSC treatment returned liver function to sham levels. ADSC upregulated the Hes1 gene and protein expression in the early and late term. Inflammation, fibrosis, and total damage scores were decreased following ADSC treatment compared with the control. Immunohistochemistry staining revealed higher CD90, CD44, and CD29 stem cell marker expression in the ADSC treatment group. Conclusions: ADSC administration reduced fibrosis and biliary damage and restored liver function, potentially in a manner mediated by upregulated Hes1 expression, supporting its promise in biliary regeneration.
Keywords: adipose-derived stem cell; biliary regeneration; bile duct ligation; Hes1 adipose-derived stem cell; biliary regeneration; bile duct ligation; Hes1
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MDPI and ACS Style

Satılmış, B.; Çiçek, E.; Karakaş, S.; Kutlutürk, K.; Kayhan, E.; Gül, M.; Otan, E.; Şahin, T.T.; Yılmaz, S. Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation. Biomedicines 2026, 14, 657. https://doi.org/10.3390/biomedicines14030657

AMA Style

Satılmış B, Çiçek E, Karakaş S, Kutlutürk K, Kayhan E, Gül M, Otan E, Şahin TT, Yılmaz S. Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation. Biomedicines. 2026; 14(3):657. https://doi.org/10.3390/biomedicines14030657

Chicago/Turabian Style

Satılmış, Basri, Egemen Çiçek, Serdar Karakaş, Koray Kutlutürk, Elif Kayhan, Mehmet Gül, Emrah Otan, Tevfik Tolga Şahin, and Sezai Yılmaz. 2026. "Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation" Biomedicines 14, no. 3: 657. https://doi.org/10.3390/biomedicines14030657

APA Style

Satılmış, B., Çiçek, E., Karakaş, S., Kutlutürk, K., Kayhan, E., Gül, M., Otan, E., Şahin, T. T., & Yılmaz, S. (2026). Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation. Biomedicines, 14(3), 657. https://doi.org/10.3390/biomedicines14030657

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