Bibliographic Details
| Title: |
Improvement of ventilator-induced lung injury by IPS cell-derived conditioned medium via inhibition of PI3K/Akt pathway and IP-10-dependent paracrine regulation |
| Authors: |
Li, Li-Fu1,2,3, Liu, Yung-Yang4,5, Yang, Cheng-Ta1,2,3, Chien, Yueh6,7, Twu, Nae-Fang8,9, Wang, Mong-Lien5, Wang, Chien-Ying9,10, Huang, Chung-Chi1,2,3, Kao, Kuo-Chin1,2,3, Hsu, Han-Shui9,10, Wu, Cheng-Wen5,9, Chiou, Shih-Hwa6,7,9 shchiou@vghtpe.gov.tw |
| Source: |
Biomaterials. Jan2013, Vol. 34 Issue 1, p78-91. 14p. |
| Subjects: |
Lung injuries, Paracrine mechanisms, Artificial respiration, Pluripotent stem cells, Transmission electron microscopy, Interferons |
| Abstract: |
Abstract: Mechanical ventilation in patients may increase the risk of an acute lung injury (ALI), termed ventilator-induced lung injury (VILI). Induced pluripotent stem cells (iPSCs) have previously been shown to improve tissue repair in different disease models, including ALI. However, the therapeutic efficacy of iPSCs-derived conditioned medium (iPSC-CM) on ALI or VILI remains unknown. Here, we demonstrated that both iPSCs and iPSC-CM effectively decrease high-tidal-volume-induced VILI-related inflammatory processes and HMGB1 and PAI-1 production, predominantly through suppressing PI3K/Akt signaling. Notably, iPSC-CM suppressed production of macrophage inflammatory protein-2, malondialdehyde, and increased total glutathione content. Transmission electron microscopy revealed that iPSC-CM potentially restored the bronchial microstructure. This iPSC-CM efficacy could be mimicked by PI3K inhibitor LY294002 or Akt heterozygous knockout, and either treatment showed no further improvement on VILI in iPSC-CM recipients. Furthermore, iPSC-CM increased interferon gamma-induced protein 10 (IP-10) production in injured lungs. Administration of IP-10-neutralizing antibodies increased neutrophil infiltration, impaired lung oxygenation and deteriorated the protective effects mediated by iPSC-CM. Our data provide a preclinical indication regarding the therapeutic potential of iPSC-CM in VILI and suggest that inhibiting PI3K/Akt pathway or increasing IP-10 is a prospective diagnostic and therapeutic target for VILI patients. [Copyright &y& Elsevier] |
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| Database: |
Engineering Source |
