Enhanced stem cell-mediated therapeutic immune modulation with zinc oxide nanoparticles in liver regenerative therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-03-04 DOI:10.1016/j.biomaterials.2025.123232

Naeun Park , Kyoung Sub Kim , Sanghee Lee , Jang Ho Choi , Kun Na

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引用次数: 0

Abstract

Liver regenerative therapy is critical for severe liver damage, including acute liver failure, fibrosis, post-cancer resection recovery, and autoimmune liver diseases, where restoration of liver tissues is essential. Stem cell-based therapies hold significant promise in liver regeneration by modulating immune responses to create a favorable healing microenvironment. However, their clinical efficacy has been limited by challenges such as poor cell engraftment and survival within the hostile injury site. To address these limitations, we developed a zinc oxide-derived nanoparticle (PZnONP) that enhances stem cell proliferation and activation by releasing bioactive Zn²⁺ and reactive oxygen species (ROS). Functionalized PZnONP exhibits pH-responsive behavior and improved dispersibility, enabling a lysosome-specific and sustained release of Zn²⁺ and ROS. Stem cells labeled with PZnONP (ZnBA) demonstrated anti-inflammatory properties, with paracrine effects influencing macrophages and damaged hepatocytes. In murine models of acute and fibrotic liver injury, it effectively migrated to the liver through stem cell homing effects and promoted anti-inflammatory responses by modulating Treg and Th17 cell polarization, as well as M2 and M1 macrophage balance, while reducing collagen synthesis. This study underscores the potential of integrating stem cell-based therapy with nanomedicine to improve regenerative outcomes in liver disease treatment.

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.