How the Pathological Microenvironment Affects the Behavior of Mesenchymal Stem Cells in the Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by fibroblasts activation, ECM accumulation, and diffused alveolar inflammation. The role of inflammation in IPF is still controversial and its involvement may follow nontraditional mechanisms. It is seen that a pathological microenvironment may affect cells, in particular mesenchymal stem cells (MSCs) that may be able to sustain the inflamed microenvironment and influence the surrounding cells. Here MSCs have been isolated from fibrotic (IPF-MSCs) and control (C-MSCs) lung tissue; first cells were characterized and compared by the expression of molecules related to ECM, inflammation, and other interdependent pathways such as hypoxia and oxidative stress. Subsequently, MSCs were co-cultured between them and with NHLF to test the effects of the cellular crosstalk. Results showed that pathological microenvironment modified the features of MSCs: IPF-MSCs, compared to C-MSCs, express higher level of molecules related to ECM, inflammation, oxidative stress, and hypoxia; notably, when co-cultured with C-MSCs and NHLF, IPF-MSCs are able to induce a pathological phenotype on the surrounding cell types. In conclusion, in IPF the pathological microenvironment affects MSCs that in turn can modulate the behavior of other cell types favoring the progression of IPF.

The possible origin of miRNAs differentially regulated in leiomyoma progenitors

“…MPCs, LPCs and AFPCs respectively isolated from healthy myometrial, broid tissue and amniotic uids met the three criteria established by the International Society for Cellular Therapy (ISCT) for the identi cation of human mesenchymal stem cells [7]. Cells were plastic-adherent in standard culture conditions, strongly positive for CD105, CD73, and CD90 and negative for CD45, CD34, CD14, CD19, and HLA-DR surface molecules and able to differentiate towards mesenchymal lineages in vitro (data not shown) [12][13][14].…”

The Possible Origin of miRNAs Differentially Regulated in Leiomyoma Progenitors

“…MPCs, LPCs and AFPCs respectively isolated from healthy myometrial, broid tissue and amniotic uids met the three criteria established by the International Society for Cellular Therapy (ISCT) for the identi cation of human mesenchymal stem cells [7]. Cells were plastic-adherent in standard culture conditions, strongly positive for CD105, CD73, and CD90 and negative for CD45, CD34, CD14, CD19, and HLA-DR surface molecules and able to differentiate towards mesenchymal lineages in vitro (data not shown) [16][17][18].…”

Mesenchymal Stem Cells Exposed to Persistently High Glucocorticoid Levels Develop Insulin-Resistance and Altered Lipolysis: A Promising In Vitro Model to Study Cushing’s Syndrome

“…The primer sequences are summarized in Table 2 . mRNA expression was calculated by the 2 −ΔΔCt method ( 21 ), where ΔCt=Ct (gene of interest)—Ct (control gene) and Δ (ΔCt)=ΔCt (differentiated MSCs)—ΔCt (undifferentiated MSCs). Genes were amplified in triplicate with the housekeeping genes RPLP0 (Ribosomal Protein Lateral Stalk Subunit P0) and GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) for data normalization.…”

“…The primer sequences are summarized in Table 2 . mRNA expression was calculated by the 2 −ΔΔCt method ( 21 ), where ΔCt=Ct (gene of interest)—Ct (control gene) and Δ (ΔCt)=ΔCt (HCE+INS+GLU)—ΔCt (LDE+INS+GLU). All selected genes were amplified in triplicate with the housekeeping genes RPLP0 and GAPDH for data normalization.…”