德国马克斯·普朗克免疫生物学和表观遗传学研究所Nina Cabezas-Wallscheid课题组研究发现，调节骨髓造血干细胞活性作为心肌梗死后的治疗策略：一项临床前研究。这一研究成果发表在2025年4月2日出版的国际学术期刊《自然—细胞生物学》上。

在这里，课题组收集了150多名心脏手术患者的胸骨BM样本，选择了49名心脏功能完好的患者。该研究组发现心肌梗死会在人骨髓造血干细胞中引起有害的转录和功能变化。谱系追踪实验表明造血干细胞是心肌梗死后促炎性髓样细胞浸润心脏组织的贡献者。在治疗上，用维生素A代谢物4-氧维甲酸来加强HSC的静止，可以抑制炎症性骨髓生成，从而调节组织重塑并保持心肌梗死后的长期心功能。

据了解，心肌梗死（MI）是一个主要的全球健康问题。尽管髓细胞在心肌梗死后紧急造血中对组织修复至关重要，但过度的髓细胞生成会加剧瘢痕形成并损害心功能。骨髓（BM）造血干细胞（HSCs）具有补充造血系统的独特能力，但其在心肌梗死后紧急造血中的作用尚未确定。

附：英文原文

Title: Modulation of bone marrow haematopoietic stem cell activity as a therapeutic strategy after myocardial infarction: a preclinical study

Author: Rettkowski, Jasmin, Romero-Mulero, Mari Carmen, Singh, Indranil, Wadle, Carolin, Wrobel, Jan, Chiang, Diana, Hoppe, Natalie, Mess, Julian, Schnberger, Katharina, Lalioti, Maria-Eleni, Jcklein, Karin, SilvaRego, Beatriz, Bhler, Timon, Karabacz, Nomie, Egg, Mirijam, Demollin, Helen, Obier, Nadine, Zhang, Yu Wei, Jlicher, Claus, Hetkamp, Anne, Czerny, Martin, Jones, Michael-Jason, Seung, Hana, Jain, Ritika, von zur Mhlen, Constantin, Maier, Alexander, Lother, Achim, Hilgendorf, Ingo, van Galen, Peter, Kreso, Antonia, Westermann, Dirk, Rodriguez-Fraticelli, Alejo E., Heidt, Timo, Cabezas-Wallscheid, Nina

Issue&Volume: 2025-04-02

Abstract: Myocardial infarction (MI) is a major global health concern. Although myeloid cells are crucial for tissue repair in emergency haematopoiesis after MI, excessive myelopoiesis can exacerbate scarring and impair cardiac function. Bone marrow (BM) haematopoietic stem cells (HSCs) have the unique capability to replenish the haematopoietic system, but their role in emergency haematopoiesis after MI has not yet been established. Here we collected human sternal BM samples from over 150 cardiac surgery patients, selecting 49 with preserved cardiac function. We show that MI causes detrimental transcriptional and functional changes in human BM HSCs. Lineage tracing experiments suggest that HSCs are contributors of pro-inflammatory myeloid cells infiltrating cardiac tissue after MI. Therapeutically, enforcing HSC quiescence with the vitamin A metabolite 4-oxo-retinoic acid dampens inflammatory myelopoiesis, thereby modulating tissue remodelling and preserving long-term cardiac function after MI.

DOI: 10.1038/s41556-025-01639-4

Source: https://www.nature.com/articles/s41556-025-01639-4