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Intrapleural delivery of MSCs attenuates acute lung injury by paracrine/endocrine mechanism.

Qin ZH, Xu JF, Qu JM, Zhang J, Sai Y, Chen CM, Wu L, Yu L - J. Cell. Mol. Med. (2012)

Bottom Line: MSCs intrapleural injection significantly improved LPS-induced lung histopathology compared with PBS-treated group at day 3.There was also a significant decrease in total cell counts and protein concentration in BALF at day 7 in the MSCs -treated rats compared to PBS control group.In conclusion, treatment with intrapleural MSCs administration markedly attenuates the severity of endotoxin-induced ALI.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

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Related in: MedlinePlus

Immunostaining levels of TNF-α and IL-4. (A) and (C) LPS induced high levels of TNF-α staining in bronchial ciliated columnar epithelial cells (red arrows) as well as in the tunica adventitia of small vessels (green arrows). MSCs treatment showed a trend towards reduction in TNF-α staining at day 3 and day 7 compared with PBS treatment group, though the difference was not significant between the two groups. (B) and (D) LPS challenge did not change the staining level of IL-4 in bronchial ciliated columnar epithelial cells (black arrows) at day 1. However, it increased significantly from day 3 to day 7. The levels of IL-4 showed no difference between the MSCs group and the PBS group. All images, ×200 magnification. Data are expressed as mean ± SD, n = 6 per group per time-point. #P < 0.05 versus normal group, ##P < 0.01 versus normal group. Data were assessed using one-way analysis of variance with SNK-q post hoc tests.
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fig09: Immunostaining levels of TNF-α and IL-4. (A) and (C) LPS induced high levels of TNF-α staining in bronchial ciliated columnar epithelial cells (red arrows) as well as in the tunica adventitia of small vessels (green arrows). MSCs treatment showed a trend towards reduction in TNF-α staining at day 3 and day 7 compared with PBS treatment group, though the difference was not significant between the two groups. (B) and (D) LPS challenge did not change the staining level of IL-4 in bronchial ciliated columnar epithelial cells (black arrows) at day 1. However, it increased significantly from day 3 to day 7. The levels of IL-4 showed no difference between the MSCs group and the PBS group. All images, ×200 magnification. Data are expressed as mean ± SD, n = 6 per group per time-point. #P < 0.05 versus normal group, ##P < 0.01 versus normal group. Data were assessed using one-way analysis of variance with SNK-q post hoc tests.

Mentions: The levels of TNF-α and another anti-inflammatory cytokine IL-4 in lung tissue were also analysed using immunostaining method. Only weak TNF-α staining was detected in bronchial ciliated columnar epithelial cells in normal lung (Fig. 9A). LPS induced a high level of TNF-α staining in bronchial ciliated columnar epithelial cells at day 1, which gradually decreased but did not reach normal level even at day 7 (Fig. 9A). Furthermore, strong staining of TNF-α located at the tunica adventitia of small vessels was also observed at day 1. However, the staining disappeared at day 7 (Fig. 9A). This finding indicated that the recovery of small vessel injury may be faster than that of bronchioles. MSCs treatment showed a trend towards reduction in TNF-α staining at day 3 and day 7 compared with PBS treatment group, although the difference was not significant between the two groups (Fig. 9C). Moderate staining of IL-4 located at bronchial ciliated columnar epithelial cells was detected in normal lung (Fig. 9B). After LPS challenge, the staining level of IL-4 did not change at day 1 (Fig. 9B). However, it increased rapidly from day 3 to day 7 (Fig. 9B). This result indicated that IL-4 may play a role in the repair of lung injury in a late phase rather than in an early phase. The difference of IL-4 was not significant between the MSCs- and PBS- treatment groups at all three time-points (Fig. 9D).


Intrapleural delivery of MSCs attenuates acute lung injury by paracrine/endocrine mechanism.

Qin ZH, Xu JF, Qu JM, Zhang J, Sai Y, Chen CM, Wu L, Yu L - J. Cell. Mol. Med. (2012)

Immunostaining levels of TNF-α and IL-4. (A) and (C) LPS induced high levels of TNF-α staining in bronchial ciliated columnar epithelial cells (red arrows) as well as in the tunica adventitia of small vessels (green arrows). MSCs treatment showed a trend towards reduction in TNF-α staining at day 3 and day 7 compared with PBS treatment group, though the difference was not significant between the two groups. (B) and (D) LPS challenge did not change the staining level of IL-4 in bronchial ciliated columnar epithelial cells (black arrows) at day 1. However, it increased significantly from day 3 to day 7. The levels of IL-4 showed no difference between the MSCs group and the PBS group. All images, ×200 magnification. Data are expressed as mean ± SD, n = 6 per group per time-point. #P < 0.05 versus normal group, ##P < 0.01 versus normal group. Data were assessed using one-way analysis of variance with SNK-q post hoc tests.
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Related In: Results  -  Collection

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fig09: Immunostaining levels of TNF-α and IL-4. (A) and (C) LPS induced high levels of TNF-α staining in bronchial ciliated columnar epithelial cells (red arrows) as well as in the tunica adventitia of small vessels (green arrows). MSCs treatment showed a trend towards reduction in TNF-α staining at day 3 and day 7 compared with PBS treatment group, though the difference was not significant between the two groups. (B) and (D) LPS challenge did not change the staining level of IL-4 in bronchial ciliated columnar epithelial cells (black arrows) at day 1. However, it increased significantly from day 3 to day 7. The levels of IL-4 showed no difference between the MSCs group and the PBS group. All images, ×200 magnification. Data are expressed as mean ± SD, n = 6 per group per time-point. #P < 0.05 versus normal group, ##P < 0.01 versus normal group. Data were assessed using one-way analysis of variance with SNK-q post hoc tests.
Mentions: The levels of TNF-α and another anti-inflammatory cytokine IL-4 in lung tissue were also analysed using immunostaining method. Only weak TNF-α staining was detected in bronchial ciliated columnar epithelial cells in normal lung (Fig. 9A). LPS induced a high level of TNF-α staining in bronchial ciliated columnar epithelial cells at day 1, which gradually decreased but did not reach normal level even at day 7 (Fig. 9A). Furthermore, strong staining of TNF-α located at the tunica adventitia of small vessels was also observed at day 1. However, the staining disappeared at day 7 (Fig. 9A). This finding indicated that the recovery of small vessel injury may be faster than that of bronchioles. MSCs treatment showed a trend towards reduction in TNF-α staining at day 3 and day 7 compared with PBS treatment group, although the difference was not significant between the two groups (Fig. 9C). Moderate staining of IL-4 located at bronchial ciliated columnar epithelial cells was detected in normal lung (Fig. 9B). After LPS challenge, the staining level of IL-4 did not change at day 1 (Fig. 9B). However, it increased rapidly from day 3 to day 7 (Fig. 9B). This result indicated that IL-4 may play a role in the repair of lung injury in a late phase rather than in an early phase. The difference of IL-4 was not significant between the MSCs- and PBS- treatment groups at all three time-points (Fig. 9D).

Bottom Line: MSCs intrapleural injection significantly improved LPS-induced lung histopathology compared with PBS-treated group at day 3.There was also a significant decrease in total cell counts and protein concentration in BALF at day 7 in the MSCs -treated rats compared to PBS control group.In conclusion, treatment with intrapleural MSCs administration markedly attenuates the severity of endotoxin-induced ALI.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary Medicine, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Show MeSH
Related in: MedlinePlus