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Therapeutic effects of mesenchymal stem cell-derived microvesicles on pulmonary arterial hypertension in rats.

Chen JY, An R, Liu ZJ, Wang JJ, Chen SZ, Hong MM, Liu JH, Xiao MY, Chen YF - Acta Pharmacol. Sin. (2014)

Bottom Line: Microvesicles (MVs) are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy.The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm.Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.

ABSTRACT

Aim: Microvesicles (MVs) are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy. In this study, we investigated the therapeutic effects of mesenchymal stem cell (MSC) derived MVs (MSC-MVs) on pulmonary artery hypertension (PAH) in rats.

Methods: MSC-MVs were isolated from rat bone marrow MSCs that were cultured in a serum-free conditioned medium. Transmission electron microscopy (TEM), flow cytometry and nanoparticle tracking analysis (NTA) were used to characterize the MVs. Adult SD rats were injected with monocrotaline (50 mg/kg, sc) to induce PAH. Three weeks later, the rats were intravenously injected with MSCs, MSC-MVs or saline for 2 weeks. At the end of treatments, the hemodynamic parameters and pathological right ventricular and pulmonary arterial remodeling were analyzed in each group.

Results: The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm. Intravenous injection of MSC-MVs or MSCs significantly ameliorated the mean pulmonary artery pressure (mPAP) and mean right ventricle pressure (mRVP) in PAH rats. Furthermore, intravenous injection of MSC-MVs or MSCs significantly decreased the right ventricle (RV) hypertrophy and pulmonary arteriole area index (AI) and thickness index (TI) in PAH rats.

Conclusion: Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.

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MSC culture and characterization. (A) A representative plot shows the fibroblast-like morphology of cultured MSCs. (B–D) Representative flow cytometry plots show the expression of CD29, but not CD31 and CD45, in cultured MSCs. Left curves, isotype control; Right curves, antibodies. (E) Osteogenic differentiation capacity of MSCs confirmed by alizarin red S staining. (F) Adipogenic differentiation capacity of MSCs determined using oil red O staining. Magnification in A, E, and F: ×10.
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fig1: MSC culture and characterization. (A) A representative plot shows the fibroblast-like morphology of cultured MSCs. (B–D) Representative flow cytometry plots show the expression of CD29, but not CD31 and CD45, in cultured MSCs. Left curves, isotype control; Right curves, antibodies. (E) Osteogenic differentiation capacity of MSCs confirmed by alizarin red S staining. (F) Adipogenic differentiation capacity of MSCs determined using oil red O staining. Magnification in A, E, and F: ×10.

Mentions: The cultured cells displayed a fibroblast-like morphology (Figure 1A). As determined by flow cytometric analysis, cultured cells positively expressed the stromal stem cell marker CD29 (Figure 1B) and negatively stained with hematopoietic lineage markers CD31 and CD45 (Figure 1C and 1D). The differentiation capacity of MSCs was revealed by the successful differentiation of MSCs into osteocytes, with calcium deposition within the cells (Figure 1E), and adipocytes, confirmed by the accumulation of lipid droplets in the vacuoles (Figure 1F).


Therapeutic effects of mesenchymal stem cell-derived microvesicles on pulmonary arterial hypertension in rats.

Chen JY, An R, Liu ZJ, Wang JJ, Chen SZ, Hong MM, Liu JH, Xiao MY, Chen YF - Acta Pharmacol. Sin. (2014)

MSC culture and characterization. (A) A representative plot shows the fibroblast-like morphology of cultured MSCs. (B–D) Representative flow cytometry plots show the expression of CD29, but not CD31 and CD45, in cultured MSCs. Left curves, isotype control; Right curves, antibodies. (E) Osteogenic differentiation capacity of MSCs confirmed by alizarin red S staining. (F) Adipogenic differentiation capacity of MSCs determined using oil red O staining. Magnification in A, E, and F: ×10.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4155533&req=5

fig1: MSC culture and characterization. (A) A representative plot shows the fibroblast-like morphology of cultured MSCs. (B–D) Representative flow cytometry plots show the expression of CD29, but not CD31 and CD45, in cultured MSCs. Left curves, isotype control; Right curves, antibodies. (E) Osteogenic differentiation capacity of MSCs confirmed by alizarin red S staining. (F) Adipogenic differentiation capacity of MSCs determined using oil red O staining. Magnification in A, E, and F: ×10.
Mentions: The cultured cells displayed a fibroblast-like morphology (Figure 1A). As determined by flow cytometric analysis, cultured cells positively expressed the stromal stem cell marker CD29 (Figure 1B) and negatively stained with hematopoietic lineage markers CD31 and CD45 (Figure 1C and 1D). The differentiation capacity of MSCs was revealed by the successful differentiation of MSCs into osteocytes, with calcium deposition within the cells (Figure 1E), and adipocytes, confirmed by the accumulation of lipid droplets in the vacuoles (Figure 1F).

Bottom Line: Microvesicles (MVs) are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy.The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm.Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.

ABSTRACT

Aim: Microvesicles (MVs) are nanoscale membrane fragments released from virtually all cell types upon activation or apoptosis, and may contribute to the beneficial effects of stem cell therapy. In this study, we investigated the therapeutic effects of mesenchymal stem cell (MSC) derived MVs (MSC-MVs) on pulmonary artery hypertension (PAH) in rats.

Methods: MSC-MVs were isolated from rat bone marrow MSCs that were cultured in a serum-free conditioned medium. Transmission electron microscopy (TEM), flow cytometry and nanoparticle tracking analysis (NTA) were used to characterize the MVs. Adult SD rats were injected with monocrotaline (50 mg/kg, sc) to induce PAH. Three weeks later, the rats were intravenously injected with MSCs, MSC-MVs or saline for 2 weeks. At the end of treatments, the hemodynamic parameters and pathological right ventricular and pulmonary arterial remodeling were analyzed in each group.

Results: The MSC-MVs showed general morphologic characteristics of MVs and expressed annexin V and CD29 markers under TEM, and their size ranged from 40 to 300 nm. Intravenous injection of MSC-MVs or MSCs significantly ameliorated the mean pulmonary artery pressure (mPAP) and mean right ventricle pressure (mRVP) in PAH rats. Furthermore, intravenous injection of MSC-MVs or MSCs significantly decreased the right ventricle (RV) hypertrophy and pulmonary arteriole area index (AI) and thickness index (TI) in PAH rats.

Conclusion: Intravenous injection of MSC-MVs or MSCs produces similar beneficial effects for treating PAH, and our results provide a basis for cell-free approach in stem cell therapy.

Show MeSH
Related in: MedlinePlus