Intratracheal Transplantation of Trophoblast Stem Cells Attenuates Acute Lung Injury in Mice

BackgroundAcute lung injury (ALI) is a common lung disorder that affects millions of people every year. The infiltration of inflammatory cells into the lungs and death of the alveolar epithelial cells are key factors to trigger a pathological cascade. Trophoblast stem cells (TSCs) have been shown to possess immune privilege, immunomodulation, and the potential of self-renewal and multipotency with differentiation into three germ layers. We hypothesized that intratracheal transplantation of TSCs may alleviate ALI.MethodsALI was induced by intratracheal delivery of Bleomycin (BLM) in mice. At day 3 after exposure to BLM, pre-labeled TSCs or Fibroblasts (FBs) were intratracheally administered into the lungs. At day 7 after exposure to BLM, histological analyses of the lungs were performed for inflammatory infiltrates, cell apoptosis, and engraftment of TSCs. Pro-inflammatory cytokines/chemokines of lung tissue and in bronchoalveolar lavage fluid (BALF) were also assessed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays , respectively. Flow cytometry was utilized to assess engraftment of TSCs and cell apoptosis.Results Histological analyses of the lungs displayed a reduction in cellularity and less thickening of the alveolar walls in ALI mice that received TSCs compared with ALI mice receiving PBS or FBs. TSCs decreased infiltration of neutrophils and macrophages, and the expression of interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived chemokine in the injured lungs. The levels of IL-6 and MCP-1 in BALF were decreased in ALI mice receiving TSCs, compared with ALI mice that received PBS or FBs. Terminal deoxynucleotidyl transferase dUTP nick end labeling confirmed that TSCs significantly reduced BLM-induced apoptosis of lung tissue in vivo and epithelial cells in vitro . Transplanted TSCs integrated into the alveolar walls and expressed aquaporin 5 and prosurfactant protein C, markers for alveolar epithelial type I and II cells, respectively. ConclusionIntratracheal transplantation of TSCs into the lungs of mice after acute exposure to BLM reduced pulmonary inflammation and cell death. Furthermore, TSCs engrafted into the alveolar walls to form alveolar epithelial type I and II cells. These data support the use of TSCs for the treatment of ALI.