明胶海绵贴片移植微冷基三维间充质干细胞缓解急性肝衰竭

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-09 DOI:10.1016/j.biomaterials.2025.123324

Haimeng Song , Xinyue Du , Yuanyuan Zhang , Wei Liu , Yi Luo , Yuxin Liu , Yongjia Xue , Mingyang Xu , Jizhen Lu , Wenwen Jia , Yanan Du , Lining Cao , Jianfeng Lu , Wencheng Zhang , Zhiying He

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引用次数: 0

摘要

人脐带间充质干细胞（human脐带mesenchymal stem cells， hUCMSCs）在肝衰竭治疗中的临床应用面临着细胞质量、移植时间短、疗效有限等挑战。本研究将明胶和戊二醛混合制备成孔径为15 ~ 36 μm的明胶微低温凝胶（GM）微载体，建立了具有较好治疗效果的hUCMSCs三维培养体系。大量RNA测序和体外实验显示，3D-hUCMSCs在与旁分泌和抗炎症相关的信号通路中表现出显著改善。这些3D-hUCMSCs不仅在旁分泌、抗氧化、抗机械力损伤等方面优于2D-hUCMSCs，而且在单细胞移植肝损伤小鼠体内时，其肝功能改善效果也优于2D-hUCMSCs。此外，开发了明胶海绵贴片嫁接（GSPG）策略，使3D-hUCMSCs能够直接植入转基因微载体中。结果表明，移植体在宿主肝脏内的整体移植效果明显改善，移植体的寿命延长。我们的研究提供了一种实用的策略，可以实现3D-hUCMSCs在明胶基质治疗急性肝衰竭中的高植入和长再训练时间。

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Gelatin sponge patch grafting of microcryogel-based three-dimensional mesenchymal stem cells to alleviate acute liver failure

The clinical application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of liver failure faces challenges due to cell quality, short engraftment time, and limited efficacy. Here, gelatin microcryogel (GM) microcarriers with pore sizes ranging from 15 to 36 μm were tuned from mixed gelatin and glutaraldehyde to develop a 3D culture system of hUCMSCs with improved therapeutic effects. Bulk RNA sequencing and in vitro assays showed that 3D-hUCMSCs exhibited significant improvement in signaling pathways related to paracrine secretion and anti-inflammation. These 3D-hUCMSCs superior compared to 2D-hUCMSCs not only in terms of paracrine secretion, protection from oxidation, and resistance to mechanical force damage, but also had better liver function improvement effect than 2D-hUCMSCs when they were transplanted as single cells into liver injury mice. Furthermore, a gelatin sponge patch grafting (GSPG) strategy was developed to enable the direct engraftment of 3D-hUCMSCs within the GM microcarriers. The results showed that overall engraftment in the host liver was significantly improved, and the life span of transplanted hosts was extended. Our study provided a practical strategy to achieve high engraftment and long retraining time of 3D-hUCMSCs in rescuing acute liver failure with gelatin matrixes.

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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.