Institute of Biomedicine, University of Turku, Turku, Finland.
Department of Plastic Surgery, Tampere University Hospital, Tampere, Finland.
Wound Repair Regen. 2023 Jan;31(1):111-119. doi: 10.1111/wrr.13047. Epub 2022 Sep 3.
Myeloid angiogenic cells (MACs) and pericyte-like cells, derived from peripheral blood mononuclear cells (MNCs) by in vitro culturing, are suggested as relevant cell types for angiogenesis and tissue repair. However, the in vivo existence and relevance of these cells has so far remained unknown. Our aim was thus to study, if MACs and pericyte-like cells exist in circulation during the wound healing of skin graft patients, and to evaluate the cellular features of wound repair. MNCs were isolated from blood samples of healthy controls (n = 4) and patients with a traumatic full thickness skin defect (n = 4) before skin grafting and on postoperative days 1 and 6. The numbers of circulating CD14 CD45 CD31 CD34 MACs and CD14 CD45 NG2 pericyte-like cells were assessed by flow cytometry, and gene expression of various pro-angiogenic factors was analysed by qPCR. Wound bed biopsies were taken on postoperative days 6 and 14, and MAC (CD31, CD14 and CD45) and pericyte-related markers (NG2 and PDGFRβ) were histologically studied. MACs and pericyte-like cells were detected in both healthy controls and in patients. Before reconstruction, on average 18% of all circulating MNCs represented MACs and 2% pericyte-like cells in wound patients. Number of MACs significantly increased 1.1-1.7-fold in all patients 1 day after skin grafting (p < 0.01). In addition, histological analysis demonstrated effective vascularization of skin grafts, as well as presence of pericytes, and CD14 and CD45 expressing myeloid cells during wound healing. In conclusion, our data shows, for the first time, the presence and mobilisation of MACs and pericyte-like cells in human circulation.
骨髓源性血管生成细胞（MACs）和周细胞样细胞，通过体外培养从外周血单核细胞（MNCs）中获得，被认为是血管生成和组织修复的相关细胞类型。然而，这些细胞在体内的存在和相关性迄今仍不清楚。因此，我们的目的是研究在皮肤移植物患者的伤口愈合过程中，MACs 和周细胞样细胞是否存在于循环中，并评估细胞修复的特征。从健康对照者（n=4）和创伤性全层皮肤缺损患者（n=4）的血液样本中分离 MNCs，在皮肤移植前和术后第 1 天和第 6 天进行分析。通过流式细胞术评估循环 CD14 CD45 CD31 CD34 MACs 和 CD14 CD45 NG2 周细胞样细胞的数量，并通过 qPCR 分析各种促血管生成因子的基因表达。在术后第 6 天和第 14 天采集伤口床活检，通过组织学研究 MAC（CD31、CD14 和 CD45）和周细胞相关标志物（NG2 和 PDGFRβ）。在健康对照者和患者中均检测到 MACs 和周细胞样细胞。在重建前，在伤口患者中，所有循环 MNCs 的平均 18%代表 MACs，而 2%代表周细胞样细胞。所有患者在皮肤移植后 1 天，MAC 数量显著增加 1.1-1.7 倍（p<0.01）。此外，组织学分析表明，皮肤移植物的有效血管化，以及周细胞、CD14 和 CD45 表达的髓样细胞在伤口愈合过程中的存在。总之，我们的数据首次表明，MACs 和周细胞样细胞存在于人类循环中，并发生了动员。
