Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches.
Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches.
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DOI：
10.1007/s13346-023-01290-2
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发表时间：
2023-07
影响因子：
5.4
通讯作者：
Rodell, Christopher B.
中科院分区：
文献类型：
--
作者：
Soni, Shreya S.;D'Elia, Arielle M.;Rodell, Christopher B.
缺血性心力衰竭（IHF）是世界范围内发病率和死亡率的主要原因，心脏移植仍然是唯一确定的治疗方法。IHF表现为心肌梗死（MI），心肌梗死启动组织重塑过程，由组织的机械变化（收缩力丧失、心肌软化）介导，这些变化与细胞机制（心肌细胞死亡、炎症反应）相互依赖。早期重塑阶段的特点是强烈的炎症，这是组织清创和修复过程启动所必需的。虽然后来向免疫再生功能的转变是可取的，但通常缺乏从炎症到修复环境的功能重新定位，使心脏处于慢性炎症状态，使心肌细胞死亡、心室扩张、过度纤维化和进行性IHF持续存在。治疗可以改变免疫微环境，包括生物治疗和基于生物材料的方法。在这篇综述中，我们概述了这些现有的方法，特别关注治疗方法（小分子药物、生物分子和细胞或细胞衍生产品）的免疫调节作用。通常侧重于免疫抑制的心脏保护策略在临床前和临床试验中显示出希望。然而，免疫再生疗法正在兴起，往往受益于加剧早期炎症。生物材料由于其固有的免疫调节特性、平行的作用机制（例如，机械约束），或通过使细胞或组织靶向递送，可用于增强这些治疗。我们进一步讨论了可翻译性和技术和程序的持续进步，这些技术和程序有助于这些迫切需要的治疗方法从实验室到床边的发展。
Ischemic heart failure (IHF) is a leading cause of morbidity and mortality worldwide, for which heart transplantation remains the only definitive treatment. IHF manifests from myocardial infarction (MI) that initiates tissue remodeling processes, mediated by mechanical changes in the tissue (loss of contractility, softening of the myocardium) that are interdependent with cellular mechanisms (cardiomyocyte death, inflammatory response). The early remodeling phase is characterized by robust inflammation that is necessary for tissue debridement and the initiation of repair processes. While later transition toward an immunoregenerative function is desirable, functional reorientation from an inflammatory to reparatory environment is often lacking, trapping the heart in a chronically inflamed state that perpetuates cardiomyocyte death, ventricular dilatation, excess fibrosis, and progressive IHF. Therapies can redirect the immune microenvironment, including biotherapeutic and biomaterial-based approaches. In this review, we outline these existing approaches, with a particular focus on the immunomodulatory effects of therapeutics (small molecule drugs, biomolecules, and cell or cell-derived products). Cardioprotective strategies, often focusing on immunosuppression, have shown promise in pre-clinical and clinical trials. However, immunoregenerative therapies are emerging that often benefit from exacerbating early inflammation. Biomaterials can be used to enhance these therapies as a result of their intrinsic immunomodulatory properties, parallel mechanisms of action (e.g., mechanical restraint), or by enabling cell or tissue-targeted delivery. We further discuss translatability and the continued progress of technologies and procedures that contribute to the bench-to-bedside development of these critically needed treatments.
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影响因子：
16.1
作者：
Bentley ER;Little SR
通讯作者：
Little SR
影响因子：
16.1
作者：
Beavers, Kelsey R.;Nelson, Christopher E.;Duvall, Craig L.
通讯作者：
Duvall, Craig L.
影响因子：
6
作者：
Hiesinger, William;Frederick, John R.;Atluri, Pavan;McCormick, Ryan C.;Marotta, Nicole;Muenzer, Jeffrey R.;Woo, Y. Joseph
通讯作者：
Woo, Y. Joseph
影响因子：
12.4
作者：
Bejarano J;Navarro-Marquez M;Morales-Zavala F;Morales JO;Garcia-Carvajal I;Araya-Fuentes E;Flores Y;Verdejo HE;Castro PF;Lavandero S;Kogan MJ
通讯作者：
Kogan MJ
影响因子：
4.9
作者：
Barth, Katrin A.;Waterfield, J. Douglas;Brunette, Donald M.
通讯作者：
Brunette, Donald M.