Human amnion epithelial cells do not abrogate pulmonary fibrosis in mice with impaired macrophage function

Sean Murphy, Suzane Chin Shiyun, Jean Tan, Siow Teng Chan, Graham Jenkin, Euan Morrison Wallace, Rebecca Seok Wai Lim

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Since current treatments for both acute and chronic lung diseases are less than ideal, there has been recent interest in the use of cell-based therapies for inflammatory lung disease. Specifically, human amnion epithelial cells (hAECs) have been shown to reduce bleomycin-induced lung injury and prevent subsequent loss of respiratory function, primarily through modulation of the host immune response. The precise mechanisms of this effect remain unclear. We aimed to investigate the potential of hAECs to mitigate bleomycin-induced lung injury in surfactant protein C deficient (Sftpc(-/-)) mice, which are highly susceptible to pulmonary injury as a result of impairment of macrophage function. Primary hAECs were administered to wild type (Sftpc(+/+)) and Sftpc(-/-) mice 24 h after exposure to bleomycin. Compared to Sftpc(+/+) mice receiving bleomycin alone, Sftpc(+/+) mice administered hAECs 24 hours after bleomycin exposure had decreased expression of proinflammatory genes, decreased macrophage and neutrophil infiltration, fibrosis, collagen content and alpha-smooth muscle actin as well as a significant improvement in lung function. Compared to Sftpc(-/-) mice given bleomycin alone, Sftpc(-/-) mice administered hAECs 24 hours after bleomycin, did not have a decrease in inflammatory gene expression or a reduction in macrophage pulmonary infiltration. Subsequently, Sftpc(-/-) mice did not show any decrease in pulmonary fibrosis or improvement of lung function after hAEC administration. The ability of hAECs to mitigate bleomycininduced lung injury is abolished in Sftpc(-/-) mice, suggesting that hAECs require normal host macrophage function to exert their reparative effects.
Original languageEnglish
Pages (from-to)1477 - 1492
Number of pages16
JournalCell Transplantation: the regenerative medicine journal
Volume21
Issue number7
DOIs
Publication statusPublished - 2012

Cite this

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title = "Human amnion epithelial cells do not abrogate pulmonary fibrosis in mice with impaired macrophage function",
abstract = "Since current treatments for both acute and chronic lung diseases are less than ideal, there has been recent interest in the use of cell-based therapies for inflammatory lung disease. Specifically, human amnion epithelial cells (hAECs) have been shown to reduce bleomycin-induced lung injury and prevent subsequent loss of respiratory function, primarily through modulation of the host immune response. The precise mechanisms of this effect remain unclear. We aimed to investigate the potential of hAECs to mitigate bleomycin-induced lung injury in surfactant protein C deficient (Sftpc(-/-)) mice, which are highly susceptible to pulmonary injury as a result of impairment of macrophage function. Primary hAECs were administered to wild type (Sftpc(+/+)) and Sftpc(-/-) mice 24 h after exposure to bleomycin. Compared to Sftpc(+/+) mice receiving bleomycin alone, Sftpc(+/+) mice administered hAECs 24 hours after bleomycin exposure had decreased expression of proinflammatory genes, decreased macrophage and neutrophil infiltration, fibrosis, collagen content and alpha-smooth muscle actin as well as a significant improvement in lung function. Compared to Sftpc(-/-) mice given bleomycin alone, Sftpc(-/-) mice administered hAECs 24 hours after bleomycin, did not have a decrease in inflammatory gene expression or a reduction in macrophage pulmonary infiltration. Subsequently, Sftpc(-/-) mice did not show any decrease in pulmonary fibrosis or improvement of lung function after hAEC administration. The ability of hAECs to mitigate bleomycininduced lung injury is abolished in Sftpc(-/-) mice, suggesting that hAECs require normal host macrophage function to exert their reparative effects.",
author = "Sean Murphy and Shiyun, {Suzane Chin} and Jean Tan and Chan, {Siow Teng} and Graham Jenkin and Wallace, {Euan Morrison} and Lim, {Rebecca Seok Wai}",
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journal = "Cell Transplantation: the regenerative medicine journal",
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Human amnion epithelial cells do not abrogate pulmonary fibrosis in mice with impaired macrophage function. / Murphy, Sean; Shiyun, Suzane Chin; Tan, Jean; Chan, Siow Teng; Jenkin, Graham; Wallace, Euan Morrison; Lim, Rebecca Seok Wai.

In: Cell Transplantation: the regenerative medicine journal, Vol. 21, No. 7, 2012, p. 1477 - 1492.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Human amnion epithelial cells do not abrogate pulmonary fibrosis in mice with impaired macrophage function

AU - Murphy, Sean

AU - Shiyun, Suzane Chin

AU - Tan, Jean

AU - Chan, Siow Teng

AU - Jenkin, Graham

AU - Wallace, Euan Morrison

AU - Lim, Rebecca Seok Wai

PY - 2012

Y1 - 2012

N2 - Since current treatments for both acute and chronic lung diseases are less than ideal, there has been recent interest in the use of cell-based therapies for inflammatory lung disease. Specifically, human amnion epithelial cells (hAECs) have been shown to reduce bleomycin-induced lung injury and prevent subsequent loss of respiratory function, primarily through modulation of the host immune response. The precise mechanisms of this effect remain unclear. We aimed to investigate the potential of hAECs to mitigate bleomycin-induced lung injury in surfactant protein C deficient (Sftpc(-/-)) mice, which are highly susceptible to pulmonary injury as a result of impairment of macrophage function. Primary hAECs were administered to wild type (Sftpc(+/+)) and Sftpc(-/-) mice 24 h after exposure to bleomycin. Compared to Sftpc(+/+) mice receiving bleomycin alone, Sftpc(+/+) mice administered hAECs 24 hours after bleomycin exposure had decreased expression of proinflammatory genes, decreased macrophage and neutrophil infiltration, fibrosis, collagen content and alpha-smooth muscle actin as well as a significant improvement in lung function. Compared to Sftpc(-/-) mice given bleomycin alone, Sftpc(-/-) mice administered hAECs 24 hours after bleomycin, did not have a decrease in inflammatory gene expression or a reduction in macrophage pulmonary infiltration. Subsequently, Sftpc(-/-) mice did not show any decrease in pulmonary fibrosis or improvement of lung function after hAEC administration. The ability of hAECs to mitigate bleomycininduced lung injury is abolished in Sftpc(-/-) mice, suggesting that hAECs require normal host macrophage function to exert their reparative effects.

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DO - 10.3727/096368911X601028

M3 - Article

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EP - 1492

JO - Cell Transplantation: the regenerative medicine journal

JF - Cell Transplantation: the regenerative medicine journal

SN - 0963-6897

IS - 7

ER -