Gonzalez-Rubio Julian, Kubiza Hannah, Xu Yong, Koenigs-Werner Hiltrud, Schmitz Mona Sophie, Schedel Michaela, Apel Christian, Jockenhoevel Stefan, Cornelissen Christian G, Thiebes Anja Lena
Department of Biohybrid & Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Forckenbeckstrasse 55, 52074, Aachen, Germany.
Institute of Pathology, Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
Adv Sci (Weinh). 2025 Apr;12(14):e2408131. doi: 10.1002/advs.202408131. Epub 2025 Jan 30.
Pericytes are a key player in vascularization, protecting endothelial cells from external harm and promoting the formation of new vessels when necessary. However, pericytic identity and its relationship with other cell types, such as mesenchymal stromal/stem cells, is highly debated. This study compares the role of pericytes and unselected stromal cells in vascularization using multichannel microfluidic chips. In both angiogenesis and vasculogenesis, pericytes promote more vessel formation than stromal cells. Pericytes can wrap around endothelial vessels acting as mural cells, while stromal cells remain separated. Whole-transcriptome sequencing confirms an upregulation of pro-vascularization genes in endothelial cell-pericyte co-cultures, while metabolism increases and inflammation decreases in stromal cell co-cultures. Treatment of stromal-endothelial cell co-cultures with either conditioned media or isolated extracellular vesicles from pericytes replicates the increase in vasculogenesis of the direct co-cultures. Cytokine quantification reveals that interleukin 6 (IL-6) is significantly increased in pericyte conditions. Blocking it with siltuximab results in a reduction of pericyte vasculogenic potential comparable to stromal cell levels, revealing that pericyte pro-vascularization is mediated by IL-6. This study provides new insights into the relationship between pericytes and endothelial cells and the elusive identity of mesenchymal stromal cells. These findings are relevant for both vascular biology and tissue engineering.
周细胞是血管生成中的关键参与者，可保护内皮细胞免受外部伤害，并在必要时促进新血管的形成。然而，周细胞的身份及其与其他细胞类型（如间充质基质/干细胞）的关系存在高度争议。本研究使用多通道微流控芯片比较了周细胞和未分选的基质细胞在血管生成中的作用。在血管生成和血管发生过程中，周细胞比基质细胞促进更多的血管形成。周细胞可以包裹在内皮血管周围，充当壁细胞，而基质细胞则保持分离。全转录组测序证实，内皮细胞-周细胞共培养中促血管生成基因上调，而基质细胞共培养中代谢增加，炎症减少。用来自周细胞的条件培养基或分离的细胞外囊泡处理基质-内皮细胞共培养物，可重现直接共培养中血管生成的增加。细胞因子定量分析显示，周细胞条件下白细胞介素6（IL-6）显著增加。用西妥昔单抗阻断它会导致周细胞血管生成潜力降低，与基质细胞水平相当，这表明周细胞的促血管生成作用是由IL-6介导的。本研究为周细胞与内皮细胞之间的关系以及间充质基质细胞难以捉摸的身份提供了新的见解。这些发现对血管生物学和组织工程都具有重要意义。
