Rosuvastatin-loaded injectable immunomodulatory hydrogel mitigates local immune response against transplanted stem cells and promotes heart repair in vivo

IF 6 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications Pub Date : 2025-08-29 DOI:10.1016/j.bioadv.2025.214481

Weiang Yan , Keshav Narayan Alagarsamy , Abhay Srivastava , Alireza Rafieerad , Rakesh C. Arora , Sanjiv Dhingra

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引用次数: 0

Abstract

In clinical trials allogeneic mesenchymal stem cells (MSCs) from young and healthy donors have shown promise to repair the heart following a heart attack. However, immune rejection of transplanted MSCs has prevented the clinical translation of stem cells-based therapies for cardiac patients. Therefore, strategies to improve survival of implanted stem cells in the heart would be of immense therapeutic value. This study presents the development of a novel immunomodulatory chitosan-rosuvastatin (CR) hydrogel loaded with MSCs for cardiac repair. The hydrogel showed excellent 3 dimensional (3D) structure and porosity, and was found to support the growth of MSCs. In an in vivo rat model of myocardial infarction (MI), the immunomodulatory CR hydrogel provided physical bulk, improved the retention of MSCs and cardiac function at 4 weeks after MI. The RNA sequencing data demonstrate that rosuvastatin improved the “stemness” of MSCs and reduced the activation of T-cells, downregulated T_H1 polarization in response to inflammatory stress in the infarcted heart. Therefore, the current study presents a new paradigm in improving clinical effectiveness of stem cell therapy for cardiac repair by modulating local immune response in the heart against transplanted stem cells using a novel immunomodulatory CR hydrogel.

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瑞舒伐他汀注射免疫调节水凝胶减轻局部免疫反应对移植干细胞和促进心脏修复在体内

在临床试验中，来自年轻健康供体的同种异体间充质干细胞（MSCs）显示出修复心脏病发作后心脏的希望。然而，移植间充质干细胞的免疫排斥反应阻碍了心脏病患者干细胞治疗的临床转化。因此，提高心脏移植干细胞存活率的策略将具有巨大的治疗价值。本研究提出了一种新型免疫调节壳聚糖-瑞舒伐他汀（CR）水凝胶装载MSCs用于心脏修复。水凝胶具有良好的三维结构和孔隙度，支持间充质干细胞的生长。在体内大鼠心肌梗死（MI）模型中，免疫调节的CR水凝胶在MI后4周提供了物理体积，改善了MSCs的保留和心功能。RNA测序数据表明，瑞舒伐他汀改善了MSCs的“干性”，降低了t细胞的激活，下调了TH1极化，以响应梗死心脏的炎症应激。因此，目前的研究提出了一种新的范例，通过使用一种新的免疫调节CR水凝胶来调节心脏对移植干细胞的局部免疫反应，从而提高干细胞治疗心脏修复的临床有效性。

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来源期刊

Materials Science & Engineering C-Materials for Biological Applications 工程技术-材料科学：生物材料

CiteScore

17.80

自引率

0.00%

发文量

501

审稿时长

27 days

期刊介绍： Biomaterials Advances, previously known as Materials Science and Engineering: C-Materials for Biological Applications (P-ISSN: 0928-4931, E-ISSN: 1873-0191). Includes topics at the interface of the biomedical sciences and materials engineering. These topics include: • Bioinspired and biomimetic materials for medical applications • Materials of biological origin for medical applications • Materials for "active" medical applications • Self-assembling and self-healing materials for medical applications • "Smart" (i.e., stimulus-response) materials for medical applications • Ceramic, metallic, polymeric, and composite materials for medical applications • Materials for in vivo sensing • Materials for in vivo imaging • Materials for delivery of pharmacologic agents and vaccines • Novel approaches for characterizing and modeling materials for medical applications Manuscripts on biological topics without a materials science component, or manuscripts on materials science without biological applications, will not be considered for publication in Materials Science and Engineering C. New submissions are first assessed for language, scope and originality (plagiarism check) and can be desk rejected before review if they need English language improvements, are out of scope or present excessive duplication with published sources. Biomaterials Advances sits within Elsevier''s biomaterials science portfolio alongside Biomaterials, Materials Today Bio and Biomaterials and Biosystems. As part of the broader Materials Today family, Biomaterials Advances offers authors rigorous peer review, rapid decisions, and high visibility. We look forward to receiving your submissions!