Smoke inhalation injury repaired by a bone marrow-derived mesenchymal stem cell paracrine mechanism: Angiogenesis involving the Notch signaling pathway

BACKGROUND: Smoke inhalation injury is an acute lung injury induced by smoke exposure characterized by vascular endothelial injury and increased permeability. Cell therapy is an attractive new therapeutic approach, although its underlying mechanism and signaling pathway remain poorly understood. We investigated the effect of systemic transplantation of preconditioned bone marrow-derived mesenchymal stem cells (BMSCs) on angiogenesis in rat model of smoke inhalation injury and explored the underlying mechanism and possible signaling pathway. METHODS: After the establishment of a smoke inhalation injury rat model, the animals were further randomized into subgroups that received either a tail vein injection of 2 x 10(6) preconditioned or nonpreconditioned BMSCs in 5-mL phosphate-buffered saline to explore the characteristics of preconditioned BMSCs, pulmonary microvessel quantities in smoke inhalation injury, and its Notch1 expression. RESULTS: BMSCs preconditioned by Co-60 gamma-ray radiation at an appropriate dose were inhibited differentiation potential in vitro without significantly affecting the paracrine activity, the ability of cell proliferation, viability, and homing. Systemic preconditioned BMSC transplantation significantly increased the quantities of microvessels in rat with smoke inhalation injury, improved the lung wet-dry weight ratio, and alleviated lung injury simply through paracrine activity. Immunofluorescence staining and Western blot analysis confirmed that the expression level of Notch(+) microvessel and Notch1 protein increased significantly after systemic transplantation. CONCLUSION: Our findings indicate that systemic transplantation of preconditioned BMSCs promotes angiogenesis through paracrine activity after smoke inhalation injury and that the Notch signaling pathway is involved in the angiogenesis process. (Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.)