Activation of canonical wnt pathway promotes differentiation of mouse bone marrow‐derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro

Abstract

The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3β and β-catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/β-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/β-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused reduced GSK 3β and β-catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI.

E-Prostanoid 2 Receptor Overexpression Promotes Mesenchymal Stem Cell Attenuated Lung Injury

“…17 Cell surface markers (CD73, CD90, CD105, and CD45) of passage 3 MSCs were determined by flow cytometry. In addition, the differentiation ability of the MSCs to the chondrogenic, osteogenic, and adipogenic lineages was also characterized.…”

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

“…Many of the insights of the function of Wnt in the context of repair processes in the lung have been identified in models of acute epithelial and lung injury, [84][85][86][87] and these studies show an important role for the canonical β-catenin-dependent Wnt pathway during repair processes in the lung. Another mechanism involved in epithelial repair is the so-called epithelial-mesenchymal transition (EMT).…”

Computational Modeling of Stem Cell Migration: A Mini Review

“…35,38 This might shed light on understanding the migration dynamics and clinical issues involved in MSCs transplantation. 18 In a therapeutic context, the most critical part of MSC transplantation is to devise a mechanism to enhance the number of transplanted cells that migrate to the site of tissue damage.…”