The controversial origin of pericytes during angiogenesis - Implications for cell-based therapeutic angiogenesis and cell-based therapies
The controversial origin of pericytes during angiogenesis - Implications for cell-based therapeutic angiogenesis and cell-based therapies
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DOI：
10.3233/ch-189132
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发表时间：
2018-01-01
影响因子：
2.1
通讯作者：
Raghunath, Michael
中科院分区：
文献类型：
--
作者：
Blocki, Anna;Beyer, Sebastian;Raghunath, Michael
周细胞位于小血管的基底膜内，经常与内皮细胞直接接触，在血管形成和体内平衡过程中发挥重要作用。最近，这些周细胞也被鉴定为间充质干细胞。间充质干细胞，特别是其特殊的周细胞亚群，代表了治疗血管生成应用的有希望的候选者，并已广泛应用于临床前和临床试验。然而，缺血性疾病（尤其是心肌梗死）的细胞治疗并没有导致显著的长期改善。有趣的是，来自造血起源的周细胞在胚胎皮肤中被观察到，在体内成人血管生成过程中描述了表达白细胞和单核细胞标记的周细胞亚群。由于间充质干细胞不表达造血标志物，后一种细胞类型可能代表与血管生成相关的另一种周细胞群。因此，我们从单核细胞中获取血源性血管生成细胞（bdac），这些细胞与造血周细胞非常相似，迄今为止仅在体内观察到。在危重肢体缺血的临床前模型中，bdac表现出许多周细胞特征，并表现出增强的血运重建和功能性组织再生。bdac与间充质周细胞的比较表明，bdac（类似于造血周细胞）促进了早期血管生成，如内皮细胞的发芽。相反，间充质周细胞负责血管的成熟和稳态，同时减少内皮细胞的发芽。由于新血管的形成在治疗性血管生成或植入物与宿主组织的整合过程中至关重要，因此造血周细胞（以及bdac）可能为基于细胞的治疗提供有利的补充甚至替代方案。
Pericytes reside within the basement membrane of small vessels and are often in direct cellular contact with endothelial cells, fulfilling important functions during blood vessel formation and homeostasis. Recently, these pericytes have been also identified as mesenchymal stem cells. Mesenchymal stem cells, and especially their specialized subpopulation of pericytes, represent promising candidates for therapeutic angiogenesis applications, and have already been widely applied in pre-clinical and clinical trials. However, cell-based therapies of ischemic diseases (especially of myocardial infarction) have not resulted in significant long-term improvement. Interestingly, pericytes from a hematopoietic origin were observed in embryonic skin and a pericyte sub-population expressing leukocyte and monocyte markers was described during adult angiogenesis in vivo. Since mesenchymal stem cells do not express hematopoietic markers, the latter cell type might represent an alternative pericyte population relevant to angiogenesis. Therefore, we sourced blood-derived angiogenic cells (BDACs) from monocytes that closely resembled hematopoietic pericytes, which had only been observed in vivo thus far. BDACs displayed many pericytic features and exhibited enhanced revascularization and functional tissue regeneration in a preclinical model of critical limb ischemia. Comparison between BDACs and mesenchymal pericytes indicated that BDACs (while resembling hematopoietic pericytes) enhanced early stages of angiogenesis, such as endothelial cell sprouting. In contrast, mesenchymal pericytes were responsible for blood vessel maturation and homeostasis, while reducing endothelial sprouting.Since the formation of new blood vessels is crucial during therapeutic angiogenesis or during integration of implants into the host tissue, hematopoietic pericytes (and therefore BDACs) might offer an advantageous addition or even an alternative for cell-based therapies.