Department of Basic Medical Sciences, Faculty of Medicine, University of La Laguna, 38071 Tenerife, Spain.
Department of Pathology, Eurofins Megalab-Hospiten Hospitals, 38100 Tenerife, Spain.
Int J Mol Sci. 2022 Aug 12;23(16):9010. doi: 10.3390/ijms23169010.
Perivascular cells in the pericytic microvasculature, pericytes and CD34+ stromal cells/telocytes (CD34+SCs/TCs), have an important role in angiogenesis. We compare the behavior of these cells depending on whether the growth of endothelial cells (ECs) from the pre-existing microvasculature is toward the interstitium with vascular bud and neovessel formation (sprouting angiogenesis) or toward the vascular lumen with intravascular pillar development and vessel division (intussusceptive angiogenesis). Detachment from the vascular wall, mobilization, proliferation, recruitment, and differentiation of pericytes and CD34+SCs/TCs, as well as associated changes in vessel permeability and functionality, and modifications of the extracellular matrix are more intense, longer lasting over time, and with a greater energy cost in sprouting angiogenesis than in intussusceptive angiogenesis, in which some of the aforementioned events do not occur or are compensated for by others (e.g., sparse EC and pericyte proliferation by cell elongation and thinning). The governing mechanisms involve cell-cell contacts (e.g., peg-and-socket junctions between pericytes and ECs), multiple autocrine and paracrine signaling molecules and pathways (e.g., vascular endothelial growth factor, platelet-derived growth factor, angiopoietins, transforming growth factor B, ephrins, semaphorins, and metalloproteinases), and other factors (e.g., hypoxia, vascular patency, and blood flow). Pericytes participate in vessel development, stabilization, maturation and regression in sprouting angiogenesis, and in interstitial tissue structure formation of the pillar core in intussusceptive angiogenesis. In sprouting angiogenesis, proliferating perivascular CD34+SCs/TCs are an important source of stromal cells during repair through granulation tissue formation and of cancer-associated fibroblasts (CAFs) in tumors. Conversely, CD34+SCs/TCs have less participation as precursor cells in intussusceptive angiogenesis. The dysfunction of these mechanisms is involved in several diseases, including neoplasms, with therapeutic implications.
周细胞存在于血管周细胞微脉管系统中，以及 CD34+基质细胞/原纤维细胞（CD34+SCs/TCs），在血管生成中起着重要作用。我们比较了这些细胞的行为，具体取决于内皮细胞（ECs）是否从预先存在的微血管中向具有血管芽和新血管形成（发芽血管生成）的间质生长，或者是否向具有血管腔内柱发育和血管分裂（内套血管生成）的血管腔生长。周细胞和 CD34+SCs/TCs 的从血管壁上分离、动员、增殖、募集和分化，以及伴随的血管通透性和功能的变化，以及细胞外基质的改变，在发芽血管生成中比在内套血管生成中更为剧烈、更为持久，并且能量消耗更大，在发芽血管生成中，上述一些事件不会发生，或者被其他事件所补偿（例如，通过细胞伸长和变薄来稀疏 EC 和周细胞的增殖）。控制机制涉及细胞-细胞接触（例如，周细胞和 EC 之间的钉和套结）、多种自分泌和旁分泌信号分子和途径（例如，血管内皮生长因子、血小板衍生生长因子、血管生成素、转化生长因子 B、ephrins、semaphorins 和金属蛋白酶）以及其他因素（例如，缺氧、血管通畅性和血流）。在发芽血管生成中，周细胞参与血管发育、稳定、成熟和退化，以及内套血管生成中柱芯的间质组织形成。在发芽血管生成中，增殖的血管周 CD34+SCs/TCs 是通过肉芽组织形成在修复期间基质细胞的重要来源，也是肿瘤中癌相关成纤维细胞（CAFs）的重要来源。相反，CD34+SCs/TCs 在内套血管生成中作为前体细胞的参与较少。这些机制的功能障碍与包括肿瘤在内的几种疾病有关，具有治疗意义。
