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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

(a) Time course of systolic arterial pressure (SBP). Indirect measurement of systolic blood pressure from day 0 until day 10 after treatment. Arrow indicates the time of transplantation. (b) Values of mean arterial pressure obtained at the end of the observation period through direct measurement of arterial blood pressure. (c) Values of heart rate of three experimental groups measured at the end of the observation period. Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.
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fig3: (a) Time course of systolic arterial pressure (SBP). Indirect measurement of systolic blood pressure from day 0 until day 10 after treatment. Arrow indicates the time of transplantation. (b) Values of mean arterial pressure obtained at the end of the observation period through direct measurement of arterial blood pressure. (c) Values of heart rate of three experimental groups measured at the end of the observation period. Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.

Mentions: Basal values of systolic arterial pressure before treatment did not differ among the groups (174.90 ± 1.3 mmHg for the saline group; 174.74 ± 0.88 mmHg for the MSC group; and 173.70 ± 1.33 mmHg for the pMSC group). However, the time course follow-up of indirect SAP measurements has shown a prolonged reduction (10 days) of tensional levels (approximately 10–15 mmHg) after i.p. administration of MSCs cultured for 72 hours in EGM-2 (Figure 3(a)). Similarly, as shown in Figure 3(b), the transplantation of pMSCs produced a significant reduction in directly recorded mean arterial blood pressure levels compared to vehicle or MSCs cultured in DMEM (146.77 ± 14.15 mmHg versus 162.22 ± 10.29 mmHg and 161.43 ± 6.63 mmHg, resp., p < 0.05). The treatments did not induce alterations in heart rate (HR) in the animals because there were no differences among the three experimental groups (Figure 3(c)).


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)

(a) Time course of systolic arterial pressure (SBP). Indirect measurement of systolic blood pressure from day 0 until day 10 after treatment. Arrow indicates the time of transplantation. (b) Values of mean arterial pressure obtained at the end of the observation period through direct measurement of arterial blood pressure. (c) Values of heart rate of three experimental groups measured at the end of the observation period. 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

fig3: (a) Time course of systolic arterial pressure (SBP). Indirect measurement of systolic blood pressure from day 0 until day 10 after treatment. Arrow indicates the time of transplantation. (b) Values of mean arterial pressure obtained at the end of the observation period through direct measurement of arterial blood pressure. (c) Values of heart rate of three experimental groups measured at the end of the observation period. Values indicated as the mean ± sem. ∗p < 0.05 versus saline; #p < 0.05 versus MSC.
Mentions: Basal values of systolic arterial pressure before treatment did not differ among the groups (174.90 ± 1.3 mmHg for the saline group; 174.74 ± 0.88 mmHg for the MSC group; and 173.70 ± 1.33 mmHg for the pMSC group). However, the time course follow-up of indirect SAP measurements has shown a prolonged reduction (10 days) of tensional levels (approximately 10–15 mmHg) after i.p. administration of MSCs cultured for 72 hours in EGM-2 (Figure 3(a)). Similarly, as shown in Figure 3(b), the transplantation of pMSCs produced a significant reduction in directly recorded mean arterial blood pressure levels compared to vehicle or MSCs cultured in DMEM (146.77 ± 14.15 mmHg versus 162.22 ± 10.29 mmHg and 161.43 ± 6.63 mmHg, resp., p < 0.05). The treatments did not induce alterations in heart rate (HR) in the animals because there were no differences among the three experimental groups (Figure 3(c)).

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