Mesenchymal cells isolated after acute lung injury manifest an enhanced proliferative phenotype.

Chen, Baruch; Polunovsky, Vitaly A.; White, James G.; Blazar, Bruce R.; Nakhleh, Raouf E.; Jessurun, José; Peterson, Mark S.; Bitterman, Peter B.

doi:10.1172/jci116052

Cited by 49 publications

(24 citation statements)

References 17 publications

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“…The adult literature suggests that mesenchymal cells may have a role in acute lung injury and persistent acute respiratory distress syndrome. [20][21][22] However, their role in neonatal lung injury has not been adequately analyzed. As ECMO is often used as a therapy for neonates with acute lung injury, our findings suggest MSCs may be isolated from newborns so to evaluate their role in the repair process of neonatal lung injury.…”

Section: Discussionmentioning

confidence: 99%

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

et al. 2010

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Objective: Endothelial progenitor cells (EPCs) have been examined in numerous adult diseases and have been suggested as a cellular-based therapy. However, there are no reports describing EPCs being isolated from newborn peripheral blood.Study Design: Endothelial colony-forming cells (ECFCs), a subtype of EPCs, were isolated from blood collected from 12 neonatal extracorporeal membrane oxygenation (ECMO) circuits.Result: ECFCs were isolated in all samples. We unexpectedly isolated a distinctly different colony of mesenchymal stem cells (MSCs) in seven samples. Both cell types expressed the expected endothelial or mesenchymal cell surface antigens. Conclusion:To our knowledge, this is the first report of ECFCs and MSCs isolated from peripheral blood of critically ill term newborns. Both cells types may be mobilized in response to critical illness or to the ECMO circuit. Further studies evaluating the role of stem cells in various newborn conditions are warranted.

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Section: Discussionmentioning

confidence: 99%

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

et al. 2010

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“…Cells were characterized as fibroblasts as described. 24 Use of human tissues was approved by the Institutional Review Board at the University of Minnesota.…”

Section: Primary Ipf and Normal Fibroblast Linesmentioning

confidence: 99%

Pathologic Caveolin-1 Regulation of PTEN in Idiopathic Pulmonary Fibrosis

Xia

Khalil

Kahm

et al. 2010

The American Journal of Pathology

138

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Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disorder refractory to current pharmacological therapies. Fibroblasts isolated from IPF patients display pathological activation of PI3K/Akt caused by low PTEN phosphatase activity. This enables these cells to escape the negative proliferative properties of polymerized collagen. The mechanism underlying low PTEN activity in IPF fibroblasts is unclear, but our prior studies indicate that membrane-associated PTEN expression is decreased in these cells. Caveolin-1 is an integral membrane protein whose expression is decreased in IPF lung tissue, but how low caveolin-1 contributes to pathological fibrosis is incompletely understood. The objective of this study was to examine the hypothesis that caveolin-1 regulates PTEN function in IPF fibroblasts. Here we demonstrate that caveolin-1 expression is a determinant of membrane PTEN levels and show that PTEN interacts with caveolin-1 via its caveolin-1-binding sequence. We demonstrate that caveolin-1 expression is low in IPF fibroblasts and that this correlates with low membrane PTEN levels , whereas overexpression of caveolin-1 restores membrane PTEN levels, inhibits Akt phosphorylation, and suppresses proliferation. We demonstrate that caveolin-1 and PTEN expression are low in myofibroblasts within IPF fibroblastic foci. These data indicate that IPF fibroblasts display low caveolin-1 expression, which results in low membrane-associated PTEN expression. This creates a membrane microenvironment depleted of inhibitory phosphatase activity, facilitating the aberrant activation PI3K/Akt and pathological proliferation. (Am J Pathol

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“…Accordingly, there are a few reports suggesting that there may be a PDGF-dependent autocrine proliferative mechanism in lung fibroblasts. Chen et al (110) showed that fibroblasts isolated from the lungs of humans (who have died of acute lung injury) proliferate in the absence of exogenous growth factors in serum-free medium, whereas those from the lungs of controls do not. Bishop et al (111) have shown that rat lung fibroblasts and a human fetal lung fibroblast cell line secrete a mesenchymal cell growth factor and proliferate when stretched on a specialized culture membrane.…”

Section: Platelet-derived Growth Factormentioning

confidence: 99%