Intrapulmonary Delivery of Human Umbilical Cord Mesenchymal Stem Cells Attenuates Acute Lung Injury by Expanding CD4+CD25+ Forkhead Boxp3 (FOXP3) + Regulatory T Cells and Balancing Anti- and Pro-inflammatory Factors

Abstract

Background: Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able to act on CD4⁺CD25⁺ Foxp3⁺Treg cells and lead to an improvement in ALI. Methods: Mice were administered intratracheally endotoxin (lipopolysaccharide [LPS]) and received intrapulmonary 1×10⁶ UCMSC 4 hours after challenge. The CD4⁺CD25⁺ Foxp3⁺Treg, survival time, body weight, histology and lung injury scores were assessed after transplantation of UCMSC. In addition, anti-inflammatory factor IL10 and pro-inflammatory mediators production including tumor necrosis factor-a (TNF-α), macrophage inflammatory protein-2(MIP-2) and interferon-γ (IFN-γ) were detected. Results: Transplantation of UCMSC resulted in significant increase in the level of CD4⁺CD25⁺ Foxp3⁺Treg in ALI. Increased level of anti-inflammatory factor IL-10 and reduced levels of TNF-α, MIP-2 and IFN-γ were simultaneously observed in ALI in comparison with control mice. Conclusion: Our data demonstrate for the first time that transplantation of UCMSC ameliorates ALI by enhancing the diminished levels of alveolar CD4⁺CD25⁺ Foxp3⁺Treg and balancing anti- and pro-inflammatory factors in ALI mice.