Prostaglandin Production and Metabolism in Self-differentiating Human Fetal Lung Organ Culture

Hume, Robert; Bell, Jeanne E.; Gourlay, Margaret; Giles, M.; Hallas, Anne; Cossar, David; Kelly, Rodney W.

doi:10.3109/01902149309064352

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…The major difference in this medium compared to the other two is the presence of prostaglandin E 2 and fibroblast growth factor. The importance of PGE 2 has been reported in fetal lung development (Hume et al ., ; McCray and Bettencourt, ). Elevating levels of PGE 2 have shown to accelerate distal epithelial differentiation.…”

Section: Resultsmentioning

confidence: 97%

“…Elevating levels of PGE 2 have shown to accelerate distal epithelial differentiation. In fetal lung cultures, prostaglandins are produced in high quantities but their levels quickly decline over time (Hume et al ., ). Not only are prostaglandins important for the regulation of airway epithelial differentiation, but they are also important for mature airway cells as well.…”

Section: Resultsmentioning

confidence: 99%

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Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration

Kokubun

Pankajakshan

Kim

et al. 2013

J Tissue Eng Regen Med

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Epithelial denudation is one of the characteristics of chronic asthma. To restore its functions, the airway epithelium has to rapidly repair the injuries and regenerate its structure and integrity. Mesenchymal stem cells (MSCs) have the ability to differentiate into many cell lineages. However, the differentiation of MSCs into epithelial cells has not been fully studied. Here, we examined the differentiation of MSCs into epithelial cells using three different media compositions with various growth supplementations. The MSCs were isolated from porcine bone marrow by density gradient centrifugation. The isolated MSCs were CD11(-) CD34(-) CD45(-) CD44(+) CD90(+) and CD105(+) by immunostaining and flow cytometry. MSCs were stimulated with EpiGRO (Millipore), BEpiCM (ScienCell) and AECGM (PromoCell) media for 5 and 10 days, and epithelial differentiation was assessed by qPCR (keratin 14, 18 and EpCAM), fluorometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM), western blot analysis (pancytokeratin, EpCAM) and flow cytometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM). The functional marker MUC1 was also assessed after 10 days of air-liquid interface (ALI) culture in optimized media. Cells cultured in BEpiCM containing fibroblast growth factor and prostaglandin E2 showed the highest expression of the epithelial markers: CK7-8 (85.90%); CK-14-15-16-19 (10.14%); and EpCAM (64.61%). The cells also expressed functional marker MUC1 after ALI culture. The differentiated MSCs when cultured in BEpiCM medium ex vivo in a bioreactor on a decellularized trachea for 10 days retained the epithelial-like phenotype. In conclusion, porcine bone marrow-derived MSCs demonstrate commitment to the epithelial lineage and might be a potential therapy for facilitating the repair of denuded airway epithelium.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration

Kokubun

Pankajakshan

Kim

et al. 2013

J Tissue Eng Regen Med

View full text Add to dashboard Cite

show abstract

“…These changes occur in sera-free media in the absence of exogenous hormones or growth factors, suggesting the presence of endogenous regulatory factors. Prostaglandins are produced in substantial amounts by human fetal lung in culture (Hume et al 1991), possibly as a result of oxidative and mechanical stresses (Hume et al 1993). Tndomethacin inhibits endogenous prostaglandin production, the process of accelerated self-development and the spontaneous induction of SP-A gene expression.…”

Section: Prostaglandinsmentioning

confidence: 99%

Lung maturation

Hume¹,

Conner²,

Gilmour³

1996

Proc. Nutr. Soc.

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Differential release of prostaglandins by organ cultures of human fetal trachea and lung

Hume

Bell

Cossar

et al. 1996

In Vitro Cell.Dev.Biol.-Animal

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Human fetal lung at 16-19 weeks gestation has a partially differentiated epithelium, and in organ culture, distal airsacs dilate and the epithelium autodifferentiates to type I and II pneumatocytes, processes regulated by endogenous prostaglandin PGE2. Human fetal trachea, at the same gestation, has a terminally differentiated mucociliary epithelium but after 4-6 d in organ culture, develops squamous metaplasia. Tracheal cultures restricted to 3 d have normal phase-contrast and light microscopy appearances and immunohistochemical reactivities (epithelium: cytokeratin 7,8,18; glutathione S-transferase pi-isozyme; epithelial membrane antigen and mesenchyme; desmin; vimentin). In human fetal trachea organ cultures, the predominant prostaglandins released are 6-keto-PGF1 alpha, PGF2 alpha, and PGE2, a pattern similar to that previously described for human adult trachea and lung. In fetal lung cultures, 13,14-dihydro-15-keto-PGF2 alpha is the major prostaglandin released with lesser amounts of 13,14-dihydro-15-keto-PFG2 alpha,PGF2 alpha,PGE2, and 6-keto-PGF1 alpha. Human fetal lung in vitro has the competence to self-differentiate, as early as 12 weeks gestation and presence of high levels in fetal lung of the inactive metabolite 13,14-dihydro-15-keto-PGE2 relative to PGE2 suggests that active prostaglandin catabolism may be one of the mechanisms to retard this stage of maturation in vivo by limiting PGE2 availability. Surprisingly, the profile of prostaglandins released from fetal lung organ culture does not change to that of a mature lung with terminal differentiation of the epithelium, and this may indicate differences in the expression of key prostaglandin-metabolizing enzymes in developing human fetal lung in culture and with in utero ontogeny.

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Prostaglandin Production and Metabolism in Self-differentiating Human Fetal Lung Organ Culture

Cited by 8 publications

References 24 publications

Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration

Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration

Lung maturation

Differential release of prostaglandins by organ cultures of human fetal trachea and lung

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