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. 2015 Jul;78(3):239-45.
doi: 10.4046/trd.2015.78.3.239. Epub 2015 Jun 30.

The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema

You-Sun Kim  1 , Ji-Young Kim  2 , Jin Won Huh  3 , Sei Won Lee  3 , Soo Jin Choi  4 , Yeon-Mok Oh  5
Affiliations

"V体育平台登录" The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema

You-Sun Kim et al. Tuberc Respir Dis (Seoul). 2015 Jul.

Abstract

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. VSports手机版.

Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only 5×10(4) MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. V体育安卓版.

Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice V体育ios版. .

Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients. VSports最新版本.

Keywords: Emphysema; Mesenchymal Stromal Cells; Therapy V体育平台登录. .

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Conflict of interest statement

Conflicts of Interest: No potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Optimal dose of mesenchymal stem cells (MSCs) to repair elastase induced emphysema in mice. C57BL/6J mice were administered 0.4 U of elastase on day 0 by intratracheal application and then intravenously injected with MSCs on day 7. Data are measures of the histological staining with hematoxylin and eosin in lung section on day 14. (A) Control (n=5), Ela (elastase only, n=15), Ela+1×104 (elastase+1×104 MSC, n=10), Ela+2.5×104 (elastase+2.5×104 MSC, n=10), Ela+5×104 (elastase+5×104 MSC, n=16), and Ela+1×105 (elastase+1×105 MSC, n=6) (×10). Scale bars=1.0 mm. (B) Morphometic analysis of the mean linear intercept. Values are presented as the mean±SEM.
Figure 2
Figure 2. The anti-apoptotic effects of mesenchymal stem cell (MSC) in elastase induced emphysema. C57BL/6J mice were intratracheally applied with 0.4 U of elastase on day 0 and then intravenously injected with MSCs on day 7. Lung tissue were collected on day 14 (n=6-9 per group). Caspase 3/7 activity was measured with fluorimetric emzymatic assay and normalized by protein concentration in lung homogenates. Ela: elastase only; Ela+5×104: elastase+5×104 MSC.
Figure 3
Figure 3. The effects on protease and anti-protease in elastase induced emphysema with or without mesenchymal stem cells (MSCs). C57BL/6J mice were intratracheally applied with 0.4 U of elastase on day 0 and then intravenously injected with MSCs on day 7. Lung tissues were collected on day 14 (n=6-9 per group). (A) Matrix metalloproteinase (MMP) 2, MMP9, and MMP12 mRNA expression were measured with quantitative polymerase chain reaction (PCR) using SYBR Green and normalized by β-actin expression and then displayed with ratio to control group. Values are presented as the mean±SEM. *p<0.05, as compared with control group. (B) Activity of MMP2 and 9 were measured with gelatin zymography. (C) The mRNA expression of SLPI (left) and tissue inhibitor of metalloproteinases-1 (TIMP1) (right) were measured with quantitative PCR using SYBR Green and normalized by β-actin expression and then displayed with ratio to control group. PBS: phosphate buffered saline; Ela: elastase only; Ela+5×104: elastase+5×104 MSC.
Figure 4
Figure 4. The production of growth factors in elastase induced emphysema with or without mesenchymal stem cells (MSCs). C57BL/6J mice were intratracheally applied with 0.4 U of elastase on day 0 and then intravenously injected with MSCs on day 7. Lung tissue were collected on day14 (n=5-9 per group). The growth factors were measured with enzyme-linked immunosorbent assay for hepatocyte growth factor (HGF) (A), fibroblast growth factor 2 (FGF2) (B), and vascular endothelial growth factor (VEGF) (C). Values are presented as the mean±SEM. *p<0.05 was statistical significance of the comparison between 2 groups. Ela: elastase only; Ela+5×104: elastase+5×104 MSC.
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V体育安卓版 - References

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