ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1579062
An Engineered Adipose Formulation Decreases Hepatic Inflammation and Fibrosis in a Rodent Model of Metabolic Dysfunction-Associated Steatotic Liver Disease
Provisionally accepted
- 1University of Maryland, Baltimore, United States
- 2Britecyte, Inc., Frederick, United States
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Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive stage metabolic dysfunction-associated steatohepatitis (MASH) represent a leading cause of liverrelated morbidity and mortality in the U.S. and worldwide. Given the high prevalence and rapid growth of MASLD, the economic and health burden, and MASH-associated morbidity and mortality, there is an unmet medical need for therapies that can stop, slow, or reverse the progression of MASLD. Adipose tissue plays a key role in metabolic health and MASLD pathogenesis through its regulation of energy metabolism and endocrine function. Metabolic dysfunction is often associated with a chronic state of low-grade inflammation in the body including adipose tissue. In this study, we tested an engineered adipose formulation (AF) composed of a combination of culture-expanded adipose stromal vascular fraction (SVF) cells and adipose tissue particulates in the treatment of MASLD. Human, rat, and mouse AFs (hAF, rAF, and mAF) showed anti-inflammatory activity, which was mediated predominantly by soluble factors present in the adipose particulate. In vivo effects of AFs were evaluated in two rodent models of MASLD: i) obese Zucker rats fed a high-fat, high-cholesterol, and high-fructose diet that mainly manifest hepatic steatosis; and ii) liver-specific CGI-58 knockout mice (LivKO) on a Western diet that display MASH pathologies. Subcutaneous implantation of hAF and rAF in obese Zucker rats significantly reduced hepatic triglycerides. In LivKO mice, mAF reduced hepatic inflammation and fibrosis, though not steatosis, as evidenced by significant decreases in hepatic M1 macrophages and mRNAs for proinflammatory and fibrogenic genes. Immunogenicity testing demonstrated that allogeneic rAF did not induce an immune response, whereas, as anticipated, xenogeneic hAF in rats triggered anti-hAF antibody formation. Despite an immune response against xenogeneic hAF, treatment of rats with hAF ameliorated hepatic steatosis. In conclusion, AF has the potential to treat MASH. Future studies focused on the optimization of AF composition, optimal dose and treatment regimen are warranted.
Keywords: Adipose Tissue, adipose stem cells, Tissue enaineering, MASLD, Fibrosis, Inflammation
Received: 18 Feb 2025; Accepted: 19 May 2025.
Copyright: © 2025 Choi, Ma, Tom, Danilkovitch and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Alla Danilkovitch, Britecyte, Inc., Frederick, United States
Liqing Yu, University of Maryland, Baltimore, United States
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