Migration versus proliferation as contributor to in vitro wound healing of vascular endothelial and smooth muscle cells

• Published in: Experimental cell research 2019-03, Vol.376 (1), p.58-66
• Main Authors: Ammann, Kaitlyn R., DeCook, Katrina J., Li, Maxwell, Slepian, Marvin J.
• Format: Article
• Language: English
• Subjects: Angioplasty; Atherectomy; Cell Movement - genetics; Cell Movement - physiology; Cell Proliferation - genetics; Cell Proliferation - physiology; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Extracellular Matrix - genetics; Extracellular Matrix - pathology; Humans; Migration; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Primary Cell Culture; Proliferation; Smooth muscle cells; Vascular; Wound healing; Wound Healing - genetics; Wound Healing - physiology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.01.011

Wound closure, as a result of collective cell growth, is an essential biological response to injury. In the field of vascular biology, the response of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to injury and substrate surface is important in therapeutic clinical treatment interventions such as angioplasty and atherectomy. Specifically, the mechanism by which cells close wounds (i.e. proliferation versus migration) in response to injury stimuli is of interest to better modulate recurrent vascular stenosis, prevent thrombus formation, occlusion, and life-threatening cardiovascular events. Here, we examine growth extent and temporal sequence of events following wound or gap introduction to a confluent monolayer of vascular SMCs or ECs. Significant differences in the preferred mechanisms of these cells to close wounds or gaps were observed; after 48 h, 73% of SMC wound closure was observed to be due to proliferation, while 75% of EC wound closure resulted from migration. These mechanisms were further modulated via addition or removal of extracellular matrix substrate and injury, with ECs more responsive to substrate composition and less to injury, in comparison to SMCs. Our results indicate that ECs and SMCs heal wounds differently, and that the time and mode of injury and associated substrate surface all impact this response. •Early wound healing (< 4 h) is migration-dominant for both ECs and SMCs.•Late endothelial cell growth (≥ 4 h) is migration-dominant.•Late smooth muscle cell growth (≥ 4 h) is proliferation-dominant.•SMC growth impacted by injury over substrate.•EC growth impacted by substrate over injury.