Engineering a dynamic extracellular matrix using thrombospondin-1 to propel hepatocyte organoids reprogramming and improve mouse liver regeneration post-transplantation

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio Pub Date : 2025-03-25 DOI:10.1016/j.mtbio.2025.101700

Zi-Yan Xu , Min Wang , Jing-Yan Shi , Ye Liu , Chao Yu , Xin-Yi Zhang , Chen-Wei Zhang , Qi-Feng He , Chao Pan , Jin Zhou , Hua Xiao , Hong-Yong Cao , Yong Ma

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引用次数: 0

Abstract

Hepatocyte organoids (HOs) hold significant potential for constructing bioartificial liver construction, toxicology research, and liver failure therapies. However, challenges such as difficulties in induced pluripotent stem cells (iPSCs) harvest and differentiation, safety concerns of tumor-derived matrices, and limited primary cell regulation hinder clinical applications. In this study, we developed a non-tumor-derived decellularized extracellular matrix (dECM) system with tunable mechanical properties and viscoelasticity to enhance stem cell proliferation and organoid functionality using thrombospondin-1 (THBS1). Nanoindentation and transcriptomic analysis revealed that THBS1 mediates adaptation and remodeling between organoids and ECM proteins, exhibiting native tissue-like viscoelasticity and up-regulated reprogramming transcriptional factors KLF4 and SOX2 via the YAP/TAZ pathway. Transplanting HOs presenting reprogramming effects into a 70 % hepatectomy model demonstrated improved liver regeneration, underscoring the potential of the THBS1-based dynamic ECM system in organoids manipulation and liver regeneration.

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来源期刊

Materials Today Bio Multiple-

CiteScore

8.30

自引率

4.90%

发文量

303

审稿时长

30 days

期刊介绍： Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).