Human Placenta Extract Declines Fat Deposition in an in Vitro Novel 3D Masld Model Publisher



Taheri P ; Majidi F ; Nouri K ; Nouri M ; Zarrabi M ; Rismani E ; Piryaei A ; Vosough M
Source: In Vitro Models Published:2026

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease, with an increasing incidence globally. Characterized by excessive lipid deposition, MASLD triggers chronic inflammation that can progress to metabolic dysfunction-associated steatohepatitis (MASH). Despite its growing burden, no approved treatment protocol exists, highlighting the need for novel therapeutic modalities. Due to lack of appropriate experimental models, research and development of innovative medications remains challenging. In this study, multicellular liver microtissues were generated by encapsulating human hepatoma (Huh-7), hepatic stellate (LX-2) and monocyte (THP-1) cell lines and umbilical vein endothelial (HUVEC) cells in a liver extracellular-derived hydrogel, mimicking the native hepatic microenvironment. MASLD pathogenesis was induced by exposing microtissues to defined concentrations of Oleic and Palmitic acids for 3 days. We evaluated the therapeutic potential of human placenta extract (hPE) on this biomimetic model. On day 4, post-MASLD-model formation, microtissues received 5 mg/ml hPE for 48 h. Assessments on day 6 showed significant improved cell viability, reduced lipid droplets, and restored hepatic synthetic functions, evidenced by enhanced albumin, alpha-fetoprotein, and urea levels. Additionally, hPE treatment declines lipid uptake and synthesis related genes (CD36 and SREBP) while upregulating fatty acid oxidation related gene (CPT1), decreased pro-inflammatory cytokines (IL-6 and TNF-α), and increased cytochrome P450 3A4 (CYP3A4) expression. Overall, hPE could alleviate MASLD complications in this bioengineered liver microtissue model and may be proposed as a potential candidate for further preclinical/clinical studies in MASLD. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2026.