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Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension.

de Oliveira LF, Almeida TR, Ribeiro Machado MP, Cuba MB, Alves AC, da Silva MV, Rodrigues Júnior V, Dias da Silva VJ - Stem Cells Int (2015)

Bottom Line: Priming of the MSCs reduced the basal cell death rate in vitro.The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups.The transplanted cells were rarely found in the hearts and kidneys.

View Article: PubMed Central - PubMed

Affiliation: Physiology Division, Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, 38025-015 Uberaba, MG, Brazil.

ABSTRACT
Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH.

No MeSH data available.


Related in: MedlinePlus

Study of endothelial function. Improvement in endothelial function was analyzed based on the percentage reduction of MAP in response to injections of different doses of acetylcholine (a). Injections of sodium nitroprusside were performed to control the endothelium-independent vasodilator response (b). Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.
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fig4: Study of endothelial function. Improvement in endothelial function was analyzed based on the percentage reduction of MAP in response to injections of different doses of acetylcholine (a). Injections of sodium nitroprusside were performed to control the endothelium-independent vasodilator response (b). Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.

Mentions: The change in blood pressure levels in response to different doses of vasorelaxant drugs acting on the vascular endothelium (acetylcholine) or vascular smooth muscle (sodium nitroprusside) allows the study of endothelial function. As shown in Figure 4, endothelial function was evaluated based on the relative decrease in arterial blood pressure in response to distinct doses of acetylcholine, and our findings showed an improvement in vasodilation response in animals treated with MSCs primed with EGM-2 medium compared to vehicle or MSCs cultured in DMEM for injections of Ach 6.25 ng/kg (22.24 ± 5.26% versus 15.17 ± 2.02% and 13.63 ± 4.84%, resp., p < 0.05) and 12.5 ng/kg (26.58 ± 5.42% versus 17.93 ± 3.79% and 20.12 ± 3.85%, resp., p < 0.05). The administration of the Ach 3.125 ng/kg dosage produced an improvement in the vasodilation response in the animals treated with pMSC compared to vehicle, but not to MSCs cultured in DMEM (16.76 ± 2.81% versus 10.76 ± 3.30%, p < 0.05; 16.76 ± 2.81% versus 12.23 ± 5.15%, p = 0.09). The Ach 25 ng/kg dosage also produced an improvement in the vasodilation response in the pMSC group, although it was not statistically significant compared with the saline or MSC group (29.71 ± 5.96 versus 25.26 ± 4.95% and 26.11 ± 4.47%, resp., p = 0.226). There were no differences between groups for all doses of sodium nitroprusside, which represents a vasodilation response that was independent of the endothelium.


Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension.

de Oliveira LF, Almeida TR, Ribeiro Machado MP, Cuba MB, Alves AC, da Silva MV, Rodrigues Júnior V, Dias da Silva VJ - Stem Cells Int (2015)

Study of endothelial function. Improvement in endothelial function was analyzed based on the percentage reduction of MAP in response to injections of different doses of acetylcholine (a). Injections of sodium nitroprusside were performed to control the endothelium-independent vasodilator response (b). Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537741&req=5

fig4: Study of endothelial function. Improvement in endothelial function was analyzed based on the percentage reduction of MAP in response to injections of different doses of acetylcholine (a). Injections of sodium nitroprusside were performed to control the endothelium-independent vasodilator response (b). Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.
Mentions: The change in blood pressure levels in response to different doses of vasorelaxant drugs acting on the vascular endothelium (acetylcholine) or vascular smooth muscle (sodium nitroprusside) allows the study of endothelial function. As shown in Figure 4, endothelial function was evaluated based on the relative decrease in arterial blood pressure in response to distinct doses of acetylcholine, and our findings showed an improvement in vasodilation response in animals treated with MSCs primed with EGM-2 medium compared to vehicle or MSCs cultured in DMEM for injections of Ach 6.25 ng/kg (22.24 ± 5.26% versus 15.17 ± 2.02% and 13.63 ± 4.84%, resp., p < 0.05) and 12.5 ng/kg (26.58 ± 5.42% versus 17.93 ± 3.79% and 20.12 ± 3.85%, resp., p < 0.05). The administration of the Ach 3.125 ng/kg dosage produced an improvement in the vasodilation response in the animals treated with pMSC compared to vehicle, but not to MSCs cultured in DMEM (16.76 ± 2.81% versus 10.76 ± 3.30%, p < 0.05; 16.76 ± 2.81% versus 12.23 ± 5.15%, p = 0.09). The Ach 25 ng/kg dosage also produced an improvement in the vasodilation response in the pMSC group, although it was not statistically significant compared with the saline or MSC group (29.71 ± 5.96 versus 25.26 ± 4.95% and 26.11 ± 4.47%, resp., p = 0.226). There were no differences between groups for all doses of sodium nitroprusside, which represents a vasodilation response that was independent of the endothelium.

Bottom Line: Priming of the MSCs reduced the basal cell death rate in vitro.The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups.The transplanted cells were rarely found in the hearts and kidneys.

View Article: PubMed Central - PubMed

Affiliation: Physiology Division, Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, 38025-015 Uberaba, MG, Brazil.

ABSTRACT
Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH.

No MeSH data available.


Related in: MedlinePlus