Implantation of MSC spheroid-derived 3D decellularized ECM enriched with the MSC secretome ameliorates traumatic brain injury and promotes brain repair

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2024-11-01 DOI:10.1016/j.biomaterials.2024.122941

Grace H. Chen , Kee-Chin Sia , Shao-Wen Liu , Ying-Chi Kao , Pei-Ching Yang , Chia-Hsin Ho , Shih-Chen Huang , Peng-Ying Lee , Min-Zong Liang , Linyi Chen , Chieh-Cheng Huang

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引用次数: 0

Abstract

Traumatic brain injury (TBI) presents substantial clinical challenges, as existing treatments are unable to reverse damage or effectively promote brain tissue regeneration. Although implantable biomaterials have been proposed to support tissue repair by mitigating the adverse microenvironment in injured brains, many fail to replicate the complex composition and architecture of the native extracellular matrix (ECM), resulting in only limited therapeutic outcomes. This study introduces an innovative approach by developing a mesenchymal stem cell (MSC) spheroid-derived three-dimensional (3D) decellularized ECM (dECM) that is enriched with the MSC-derived matrisome and secretome, offering a promising solution for TBI treatment and brain tissue regeneration. Proteomic and cytokine array analyses revealed that 3D dECM retained a diverse array of MSC spheroid-derived matrisome proteins and secretome components, which are crucial for replicating the complexity of native ECM and the therapeutic capabilities of MSCs. These molecules were found to underlie the observed effects of 3D dECM on immunomodulation, proneuritogenesis, and proangiogenesis in our in vitro functional assays. Implantation of 3D dECM into TBI model mice effectively mitigated postinjury tissue damage and promoted brain repair, as evidenced by a reduced brain lesion volume, decreased cell apoptosis, alleviated neuroinflammation, reduced glial scar formation, and increased of neuroblast recruitment to the lesion site. These outcomes culminated in improved motor function recovery in animals, highlighting the multifaceted therapeutic potential of 3D dECM for TBI. In summary, our study elucidates the transformative potential of MSC spheroid-derived bioactive 3D dECM as an implantable biomaterial for effectively mitigating post-TBI neurological damage, paving the way for its broader therapeutic application.

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植入富含间充质干细胞分泌组的间充质干细胞球衍生三维脱细胞ECM可改善创伤性脑损伤并促进脑修复。

创伤性脑损伤（TBI）给临床带来了巨大挑战，因为现有的治疗方法无法逆转损伤或有效促进脑组织再生。虽然有人提出植入式生物材料可通过缓解受伤大脑中的不利微环境来支持组织修复，但许多生物材料无法复制原生细胞外基质（ECM）的复杂成分和结构，导致治疗效果有限。本研究引入了一种创新方法，即开发一种间充质干细胞（MSC）球体衍生的三维（3D）脱细胞ECM（dECM），该ECM富含间充质干细胞衍生的基质组（MSC-derived matrisome）和分泌组（Secretome），为创伤性脑损伤治疗和脑组织再生提供了一种前景广阔的解决方案。蛋白质组和细胞因子阵列分析表明，三维 dECM 保留了多种间充质干细胞球衍生的基质组蛋白和分泌组成分，这对于复制原生 ECM 的复杂性和间充质干细胞的治疗能力至关重要。在我们的体外功能测试中，我们发现这些分子是三维 dECM 对免疫调节、促泌尿素生成和促血管生成的观察效应的基础。将三维 dECM 植入创伤性脑损伤模型小鼠体内可有效减轻伤后组织损伤并促进脑修复，具体表现为脑损伤体积缩小、细胞凋亡减少、神经炎症减轻、胶质瘢痕形成减少以及病变部位神经母细胞募集增加。这些结果最终改善了动物的运动功能恢复，凸显了三维 dECM 对创伤性脑损伤的多方面治疗潜力。总之，我们的研究阐明了间充质干细胞球体衍生的生物活性三维 dECM 作为一种可植入的生物材料在有效缓解创伤后神经损伤方面的变革潜力，为其更广泛的治疗应用铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.