Blockade of TSP-1/CD47 signal axis promotes donor hematopoietic engraftment by improving SEC/MK niche function

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-02-04 DOI:10.1016/j.isci.2025.111952

Feng Wang , Yan-Hou Liu , Ting Zhang , Xintong Hou , Yanbao Xin , Guang-Yao Xie , Wen-Jie Zhao , Xue Wang , Tianmeng Sun , Zheng Hu , Yong-Guang Yang

{"title":"Blockade of TSP-1/CD47 signal axis promotes donor hematopoietic engraftment by improving SEC/MK niche function","authors":"Feng Wang , Yan-Hou Liu , Ting Zhang , Xintong Hou , Yanbao Xin , Guang-Yao Xie , Wen-Jie Zhao , Xue Wang , Tianmeng Sun , Zheng Hu , Yong-Guang Yang","doi":"10.1016/j.isci.2025.111952","DOIUrl":null,"url":null,"abstract":"<div><div>Thrombospondin-1 (TSP-1)/CD47 signaling induces cell death and inhibits angiogenesis. Here, we investigated the possibility of improving donor engraftment by blocking the TSP-1/CD47 pathway in mouse models of total body irradiation (TBI)-conditioned syngeneic hematopoietic stem cell transplantation (HSCT). Our findings revealed that HSCT engraftment was improved in mice deficient in CD47 (Cd47−/−) or TSP-1 (Thbs1−/−) compared to wild-type (WT) mice. The lack of TSP-1 or CD47 enhanced the production of CXCL12 by megakaryocytes and platelets, promoting the seeding of donor hematopoietic stem cells (HSCs) in sinusoidal endothelial cell (SEC)/megakaryocyte niches. Both Cd47−/− and Thbs1−/− mice showed reduced platelet adhesion to sinusoidal vascular cells, attenuated endothelial injury, and enhanced BM vascular regeneration, preserving SEC niches. Antibody neutralization of TSP-1 significantly increased CXCL12 production, donor HSC engraftment, and vascular niche regeneration in WT mice. In summary, the TSP-1/CD47 pathway is a promising therapeutic target to enhance HSCT efficacy and reduce endothelial injury syndrome.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111952"},"PeriodicalIF":4.6000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225002123","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Thrombospondin-1 (TSP-1)/CD47 signaling induces cell death and inhibits angiogenesis. Here, we investigated the possibility of improving donor engraftment by blocking the TSP-1/CD47 pathway in mouse models of total body irradiation (TBI)-conditioned syngeneic hematopoietic stem cell transplantation (HSCT). Our findings revealed that HSCT engraftment was improved in mice deficient in CD47 (Cd47^−/−) or TSP-1 (Thbs1^−/−) compared to wild-type (WT) mice. The lack of TSP-1 or CD47 enhanced the production of CXCL12 by megakaryocytes and platelets, promoting the seeding of donor hematopoietic stem cells (HSCs) in sinusoidal endothelial cell (SEC)/megakaryocyte niches. Both Cd47^−/− and Thbs1^−/− mice showed reduced platelet adhesion to sinusoidal vascular cells, attenuated endothelial injury, and enhanced BM vascular regeneration, preserving SEC niches. Antibody neutralization of TSP-1 significantly increased CXCL12 production, donor HSC engraftment, and vascular niche regeneration in WT mice. In summary, the TSP-1/CD47 pathway is a promising therapeutic target to enhance HSCT efficacy and reduce endothelial injury syndrome.

Abstract Image

查看原文本刊更多论文

血栓软蛋白-1（TSP-1）/CD47 信号传导会诱导细胞死亡并抑制血管生成。在此，我们研究了通过阻断全身照射（TBI）条件下合成造血干细胞移植（HSCT）小鼠模型中的TSP-1/CD47通路来改善供体移植的可能性。我们的研究结果表明，与野生型（WT）小鼠相比，CD47（Cd47-/-）或TSP-1（Thbs1-/-）缺乏的小鼠造血干细胞移植效果更好。缺乏TSP-1或CD47会增强巨核细胞和血小板产生的CXCL12，促进供体造血干细胞（HSCs）在窦状内皮细胞（SEC）/巨核细胞龛位中播种。Cd47-/-小鼠和Thbs1-/-小鼠均显示血小板对窦状血管细胞的粘附减少，内皮损伤减轻，BM血管再生增强，SEC壁龛得以保留。抗体中和 TSP-1 能显著增加 CXCL12 的产生、供体造血干细胞的移植以及 WT 小鼠血管龛的再生。总之，TSP-1/CD47 通路是一种很有前景的治疗靶点，可提高造血干细胞移植的疗效并减少内皮损伤综合征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.