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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

Phase-contrast micrographs of MSCs in culture (Panel (a)), showing the typical fibroblastoid morphology. Differentiation of MSCs, which were cultured in osteogenic and adipogenic medium as previously described. Calcium deposited in the extracellular matrix is stained red by Alizarin Red (Panel (b)). Lipid vacuoles are stained orange with Oil Red O (Panel (c)). Magnifications, ×100 (Panels (a)–(c)). (Panel (d)) Immunophenotypic profile of MSCs cultured in conventional medium. Flow cytometry expression of selected molecules (CD11b, CD117(cKit), CD45, CD34, CD31 and CD29) by MSC population.
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fig1: Phase-contrast micrographs of MSCs in culture (Panel (a)), showing the typical fibroblastoid morphology. Differentiation of MSCs, which were cultured in osteogenic and adipogenic medium as previously described. Calcium deposited in the extracellular matrix is stained red by Alizarin Red (Panel (b)). Lipid vacuoles are stained orange with Oil Red O (Panel (c)). Magnifications, ×100 (Panels (a)–(c)). (Panel (d)) Immunophenotypic profile of MSCs cultured in conventional medium. Flow cytometry expression of selected molecules (CD11b, CD117(cKit), CD45, CD34, CD31 and CD29) by MSC population.

Mentions: Characterization of the stem cells investigated in the present study was performed as indicated by the International Society for Stem Cell Therapy and the Mesenchymal and Tissue Stem Cell Committee [7]. The MSCs exhibited all of their defining characteristics, such as plastic adherence capability, fibroblastoid format (Figure 1(a)), and in vitro osteogenic and adipogenic differentiation using specific differentiation medium demonstrating their multipotential properties (Figures 1(b) and 1(c)). As expected, MSCs presented the immunophenotype consistent with the accepted definition, namely, CD45−, CD29+, CD117−, CD31−, CD11b−, and CD34−; then, cell culture contamination with hematopoietic stem cells, leukocytes, endothelial cells, and macrophages was eliminated (Figure 1(d)).


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)

Phase-contrast micrographs of MSCs in culture (Panel (a)), showing the typical fibroblastoid morphology. Differentiation of MSCs, which were cultured in osteogenic and adipogenic medium as previously described. Calcium deposited in the extracellular matrix is stained red by Alizarin Red (Panel (b)). Lipid vacuoles are stained orange with Oil Red O (Panel (c)). Magnifications, ×100 (Panels (a)–(c)). (Panel (d)) Immunophenotypic profile of MSCs cultured in conventional medium. Flow cytometry expression of selected molecules (CD11b, CD117(cKit), CD45, CD34, CD31 and CD29) by MSC population.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Phase-contrast micrographs of MSCs in culture (Panel (a)), showing the typical fibroblastoid morphology. Differentiation of MSCs, which were cultured in osteogenic and adipogenic medium as previously described. Calcium deposited in the extracellular matrix is stained red by Alizarin Red (Panel (b)). Lipid vacuoles are stained orange with Oil Red O (Panel (c)). Magnifications, ×100 (Panels (a)–(c)). (Panel (d)) Immunophenotypic profile of MSCs cultured in conventional medium. Flow cytometry expression of selected molecules (CD11b, CD117(cKit), CD45, CD34, CD31 and CD29) by MSC population.
Mentions: Characterization of the stem cells investigated in the present study was performed as indicated by the International Society for Stem Cell Therapy and the Mesenchymal and Tissue Stem Cell Committee [7]. The MSCs exhibited all of their defining characteristics, such as plastic adherence capability, fibroblastoid format (Figure 1(a)), and in vitro osteogenic and adipogenic differentiation using specific differentiation medium demonstrating their multipotential properties (Figures 1(b) and 1(c)). As expected, MSCs presented the immunophenotype consistent with the accepted definition, namely, CD45−, CD29+, CD117−, CD31−, CD11b−, and CD34−; then, cell culture contamination with hematopoietic stem cells, leukocytes, endothelial cells, and macrophages was eliminated (Figure 1(d)).

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