Field-Corbett, Ciara and O'Dea, Shirley
Soluble Signals from Mechanically Disrupted Lung
Tissue Induce Lung-Related Gene Expression in
Bone Marrow-Derived Cells In Vitro.
Stem Cells and Development, 16 (XXX-XXX).
Differentiation of bone marrow (BM)-derived cells into lung epithelial cells has been reported in vivo
in animal models of lung injury. Most studies have used cytokeratin or surfactant protein expression
as markers of BM-to-lung cell differentiation. However, concerns as to whether fusion rather than differentiation
is the mechanism involved, verification of BM-derived lung cells, and inconsistent findings
with different injury models mean that the differentiation potential of BM-derived cells remains unclear.
We used a co-culture system, in which BM cell–lung cell fusion is prevented, to examine the ability
of ‘damage’ signals released from mechanically disrupted lung tissue to induce expression of lungrelated
genes in BM-derived cells in vitro. BM-derived hematopoietic progenitor cells (BM-HPCs) were
co-cultured with mechanically disrupted lung tissue. Liver tissue and medium-only co-cultures were
also studied as controls. BM-HPCs differentiated into myeloid cells in culture. BM-HPCs proliferated
in response to soluble lung damage signals and differentiated into suspension and adherent populations
with dendritic cell- and Langerhans cell-like characteristics, respectively. Induction or up-regulation of
cytokeratins 7 and 18 and surfactant protein B mRNA expression occurred in the suspension, dendritic
cell (DC)-like population during co-culture with lung tissue. In contrast, these genes were not induced
or up-regulated in medium-only or liver co-cultures. Up-regulation of E-cadherin mRNA and protein
expression also occurred in response to lung damage signals. These results confirm that signals released
from damaged lung tissue can induce lung-related gene expression in BM-derived DC-like cells in the
absence of cell fusion.
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