Tissue-Resident Mesenchymal Stem/stromal Cells (MSC) Modulate the Angiogenic Processes in Brain Arteriovenous Malformations (bAVM).

IF 4.2 3区医学 Q2 CELL & TISSUE ENGINEERING

Stem Cell Reviews and Reports Pub Date : 2025-07-17 DOI:10.1007/s12015-025-10937-1

Claudia Alexandra Dumitru, Belal Neyazi, Tamer Ayberk Kaya, Klaus-Peter Stein, Ali Rashidi, Christian Mawrin, Ibrahim Erol Sandalcioglu

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Abstract

Background: Mesenchymal stem/stromal cells (MSCs) have been mainly studied in the context of cell-based therapy for a variety of medical conditions, including cerebrovascular diseases. However, the role of tissue-resident MSCs in the pathophysiology of cerebrovascular diseases in general and of brain arteriovenous malformation (bAVM) in particular is currently unknown, and was investigated in this study.

Methods: Human bAVM tissues were used to identify MSCs in situ (n = 10) and to isolate them ex vivo (n = 3). The paracrine effects of bAVM-MSCs on endothelial cells (ECs) were assessed in an ex vivo model using MSC-derived supernatants (SNs) and the EC line HUVEC. Selected functional assays were validated using a second EC line (HCAEC).

Results: In situ, cells with a MSC-like phenotype (CD90^posCD105^posCD73^pos) were found in 7 out of 10 bAVM tissues analysed. Ex vivo, MSCs were isolated from fresh bAVM samples and were subsequently characterized according to the ISCT^® criteria. The bAVM-MSC SNs had no effect on the ECs' migration, but promoted the proliferation of the ECs. The strongest stimulatory effect of the bAVM-MSC SNs was observed regarding the ECs' tubulogenesis. Additionally, the bAVM-MSC SN induced a partial endothelial-to-mesenchymal transition in ECs.

Conclusions: These findings indicate that bAVMs contain tissue-resident MSCs, which can potentially modulate the biology and functions of the ECs in the bAVM microenvironment. Thus, MSCs may play critical roles in the pathophysiology and the progression of this disease.

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组织常驻间充质干细胞/基质细胞（MSC）调节脑动静脉畸形（bAVM）的血管生成过程。

背景：间充质干细胞（MSCs）主要是在包括脑血管疾病在内的多种疾病的细胞治疗背景下研究的。然而，组织驻留MSCs在脑血管疾病，特别是脑动静脉畸形（bAVM）的病理生理中的作用目前尚不清楚，本研究对其进行了研究。方法：采用人bam组织原位鉴定MSCs （n = 10）和离体分离MSCs （n = 3）。在体外模型中，利用msc衍生的上清液（SNs）和EC系HUVEC评估了bAVM-MSCs对内皮细胞（ECs）的旁分泌作用。选择的功能分析使用第二条EC线（HCAEC）进行验证。结果：在原位，在分析的10个bAVM组织中有7个发现具有msc样表型（CD90posCD105posCD73pos）的细胞。在体外，从新鲜的bAVM样品中分离MSCs，随后根据ISCT®标准进行表征。bam - msc对ECs的迁移没有影响，但促进了ECs的增殖。在内皮细胞的小管形成方面，观察到bam - msc SNs的最强刺激作用。此外，bAVM-MSC SN在ECs中诱导了部分内皮细胞向间质细胞的转变。结论：这些发现表明，bAVM中含有组织驻留MSCs，其可能调节bAVM微环境中ECs的生物学和功能。因此，间充质干细胞可能在该疾病的病理生理和进展中发挥关键作用。

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

Stem Cell Reviews and Reports 医学-细胞生物学

CiteScore

9.30

自引率

4.20%

发文量

审稿时长

3 months

期刊介绍： The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication: i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field. ii) full length and short reports presenting original experimental work. iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics. iv) papers focused on diseases of stem cells. v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale. vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research. vii) letters to the editor and correspondence. In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on: i) the role of adult stem cells in tissue regeneration; ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development; iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells; iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis; v) the role of stem cells in aging processes and cancerogenesis.