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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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Related in: MedlinePlus

MSC-MVs and MSCs alleviate mPAP and mRVP in PAH rats. (A1–A4) Representative traces show the mPAP and mRVP in control, vehicle, MSC, and MSC-MV groups. (B and C) Summarized data of mPAP and mRVP in different groups. Data are expressed as the mean±SEM. n=7/group. cP<0.01 vs control. fP<0.01 vs vehicle. mPAP, mean pulmonary artery pressure; mRVP, mean right ventricle pressure; RV, right ventricle; PAH, pulmonary artery hypertension.
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fig3: MSC-MVs and MSCs alleviate mPAP and mRVP in PAH rats. (A1–A4) Representative traces show the mPAP and mRVP in control, vehicle, MSC, and MSC-MV groups. (B and C) Summarized data of mPAP and mRVP in different groups. Data are expressed as the mean±SEM. n=7/group. cP<0.01 vs control. fP<0.01 vs vehicle. mPAP, mean pulmonary artery pressure; mRVP, mean right ventricle pressure; RV, right ventricle; PAH, pulmonary artery hypertension.

Mentions: At week 5 after MCT injection, pulmonary hemodynamics were measured in all rats. Representative pressure curves of mPAP and mRVP are shown in Figure 3A1-3A4. The PAH model was produced successfully as revealed by a higher mPAP in the vehicle group than in the control group (P<0.01; n=7/group). Also, mPAP was attenuated in the MSC-MV and MSC groups compared to the vehicle group but was higher than that in the control group (P<0.01; n=7/group) (Figure 3B). There was no difference in mPAP between the MSC and MSC-MV groups (P>0.05; n=7/group). Similarly, mRVP was lower in the MSC-MV and MSC groups than that in the vehicle group but was higher than that in the control group (P<0.01; n=7/group). Also, there was no significant difference in these variables between the MSC and MSC-MV groups (P>0.05; n=7/group).


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-MVs and MSCs alleviate mPAP and mRVP in PAH rats. (A1–A4) Representative traces show the mPAP and mRVP in control, vehicle, MSC, and MSC-MV groups. (B and C) Summarized data of mPAP and mRVP in different groups. Data are expressed as the mean±SEM. n=7/group. cP<0.01 vs control. fP<0.01 vs vehicle. mPAP, mean pulmonary artery pressure; mRVP, mean right ventricle pressure; RV, right ventricle; PAH, pulmonary artery hypertension.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: MSC-MVs and MSCs alleviate mPAP and mRVP in PAH rats. (A1–A4) Representative traces show the mPAP and mRVP in control, vehicle, MSC, and MSC-MV groups. (B and C) Summarized data of mPAP and mRVP in different groups. Data are expressed as the mean±SEM. n=7/group. cP<0.01 vs control. fP<0.01 vs vehicle. mPAP, mean pulmonary artery pressure; mRVP, mean right ventricle pressure; RV, right ventricle; PAH, pulmonary artery hypertension.
Mentions: At week 5 after MCT injection, pulmonary hemodynamics were measured in all rats. Representative pressure curves of mPAP and mRVP are shown in Figure 3A1-3A4. The PAH model was produced successfully as revealed by a higher mPAP in the vehicle group than in the control group (P<0.01; n=7/group). Also, mPAP was attenuated in the MSC-MV and MSC groups compared to the vehicle group but was higher than that in the control group (P<0.01; n=7/group) (Figure 3B). There was no difference in mPAP between the MSC and MSC-MV groups (P>0.05; n=7/group). Similarly, mRVP was lower in the MSC-MV and MSC groups than that in the vehicle group but was higher than that in the control group (P<0.01; n=7/group). Also, there was no significant difference in these variables between the MSC and MSC-MV groups (P>0.05; n=7/group).

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