Electrophysiological Maturation of Rat Mesenchymal Stem Cells after Induction of Vascular Smooth Muscle Cell Differentiation In Vitro

Bonnet, Pierre; Awede, Bonaventure; Rochefort, Gaël Y.; Mirza, Alain; Lermusiaux, Patrick; Domenech, Jorge; Eder, Véronique

doi:10.1089/scd.2007.0219

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…We previously obtained, in a rat model, restoration of a multilayer media using bone marrow mesenchymal stem cells self-expanded on a vascular prosthetic patch and placed in vivo on a descending aorta [16,17]. We demonstrated here an additional effect of rh-BMP2 on BM-MSCs that allowed vascular regeneration by providing three layered-walls that resemble adult artery.…”

Section: Discussionmentioning

confidence: 80%

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Regeneration of Three Layers Vascular Wall by using BMP2-Treated MSC Involving HIF-1α and Id1 Expressions Through JAK/STAT Pathways

Belmokhtar

Bourguignon

Khamis

et al. 2011

Stem Cell Rev and Rep

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Engineering living, multilayered blood vessels to form in vivo arteries is a promising alternative to peripheral artery bypass using acellular grafts restricted by thrombosis and occlusion at long term. Bone Morphogenetic Protein 2 (BMP2) is a growth factor determining in the early vascular embryonic development. The aim of the present study was evaluate the collaborative effect of recombinant human--BMP2 and Bone marrow--Mesenchymal stem cells (BM-MSCs) seeded on vascular patch to regenerate a vascular arterial wall in a rat model. BM-MSCs expressing green fluorescent protein (GFP) seeded on vascular patch were cultured in presence of recombinant human-BMP2 [100 ng/mL] during 1 week before their implantation on the abdominal aorta of Wistar rats. We observed after 2 weeks under physiological arterial flow a regeneration of a three layers adult-like arterial wall with a middle layer expressing smooth muscle proteins and a border layer expressing endothelial marker. In vitro study, using Matrigel assay and co-culture of BM-MSCs with endothelial cells demonstrated that rh-BMP2 promoted tube-like formation even at long term (90 days) allowing the organization of thick rails. We demonstrated using inhibitors and siRNAs that rh-BMP2 enhanced the expression of HIF-1α and Id1 through, at least in part, the stimulation of JAK2/STAT3/STAT5 signaling pathways. Rh-BMP2 by mimicking embryological conditions allowed vascular BM-MSCs differentiation.

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Section: Discussionmentioning

confidence: 80%

“…Cell isolation and culture procedures for BM-MSCs have been established and published previously [16,17]. Briefly, femurs were aseptically harvested from 6-to 8-week-old of genetically modified Wistar rats for over expressing green fluorescent protein (GFP) and the adherent soft tissue was removed.…”

Section: Bone Marrow-mesenchymal Stem Cellsmentioning

confidence: 99%

Regeneration of Three Layers Vascular Wall by using BMP2-Treated MSC Involving HIF-1α and Id1 Expressions Through JAK/STAT Pathways

Belmokhtar

Bourguignon

Khamis

et al. 2011

Stem Cell Rev and Rep

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“…SMCs are highly specialized cells whose principal functions are contraction and relaxation, and previously induced bone marrow mesenchymal stem cells (BMSCs) were able to acquire a similar electrophysiological profile to SMCs. In vitro differentiation of BMSCs (52, 53) induced an enhancement of the I KCa current, but, despite specific SM protein expression and modification of electrophysiological properties, bona fide differentiated MSCs failed to display contractile properties. These results have underscored the necessity to find the ideal culture conditions to induce a complete developed SMC functionality (52, 53).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro differentiation of BMSCs (52, 53) induced an enhancement of the I KCa current, but, despite specific SM protein expression and modification of electrophysiological properties, bona fide differentiated MSCs failed to display contractile properties. These results have underscored the necessity to find the ideal culture conditions to induce a complete developed SMC functionality (52, 53). We demonstrated here that only SMhAFSCs presented functional properties of mature SMCs with characteristics resembling human SMCs.…”

Section: Discussionmentioning

confidence: 99%

Human amniotic fluid stem cell differentiation along smooth muscle lineage

et al. 2013

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Functional smooth muscle engineering requires isolation and expansion of smooth muscle cells (SMCs), and this process is particularly challenging for visceral smooth muscle tissue where progenitor cells have not been clearly identified. Herein we showed for the first time that efficient SMCs can be obtained from human amniotic fluid stem cells (hAFSCs). Clonal lines were generated from c-kit(+) hAFSCs. Differentiation toward SM lineage (SMhAFSCs) was obtained using a medium conditioned by PDGF-BB and TGF-β1. Molecular assays revealed higher level of α smooth muscle actin (α-SMA), desmin, calponin, and smoothelin in SMhAFSCs when compared to hAFSCs. Ultrastructural analysis demonstrated that SMhAFSCs also presented in the cytoplasm increased intermediate filaments, dense bodies, and glycogen deposits like SMCs. SMhAFSC metabolism evaluated via mass spectrometry showed higher glucose oxidation and an enhanced response to mitogenic stimuli in comparison to hAFSCs. Patch clamp of transduced hAFSCs with lentiviral vectors encoding ZsGreen under the control of the α-SMA promoter was performed demonstrating that SMhAFSCs retained a smooth muscle cell-like electrophysiological fingerprint. Eventually SMhAFSCs contractility was evident both at single cell level and on a collagen gel. In conclusion, we showed here that hAFSCs under selective culture conditions are able to give rise to functional SMCs.

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“…Another function of the niches is to regulate hematopoietic stem/ progenitor cell (HSPC) trafficking into the blood stream. The main cellular component of the hematopoietic microenvironment is represented by cells usually referred to as mesenchymal stromal cells (MSCs) or mesenchymal stem cells [2,3], which display a vascular smooth muscle phenotype [4,5] and reside in the bone marrow (BM), where they give rise to the mesenchymal lineages, including adipogenic, osteogenic, and chondrogenic pathways. Previous studies have suggested that a subset of osteoblasts is a key constitutive element for the control of HSC stemness [6,7], whereas vascular cells (mural and endothelial cells) might control HSPC proliferation and differentiation [8].…”

Section: Introductionmentioning

confidence: 99%

Granulocyte-Colony-Stimulating Factor Stimulation of Bone Marrow Mesenchymal Stromal Cells Promotes CD34+ Cell Migration Via a Matrix Metalloproteinase-2-Dependent Mechanism

Ponte

Ribeiro-Fleury

Chabot

et al. 2012

Stem Cells and Development

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Human hematopoietic stem/progenitor cells (HSPCs) can be mobilized into the circulation using granulocytecolony stimulating factor (G-CSF), for graft collection in view of hematopoietic transplantation. This process has been related to bone marrow (BM) release of serine proteases and of the matrix metalloproteinase-9 (MMP-9). Yet, the role of these mediators in HSC egress from their niches remains questionable, because they are produced by nonstromal cells (mainly neutrophils and monocytes/macrophages) that are not a part of the niche. We show here that the G-CSF receptor (G-CSFR) is expressed by human BM mesenchymal stromal/stem cells (MSCs), and that G-CSF prestimulation of MSCs enhances the in vitro trans-stromal migration of CD34 + cells. Zymography analysis indicates that pro-MMP-2 (but not pro-MMP-9) is expressed in MSCs, and that G-CSF treatment increases its expression and induces its activation at the cell membrane. We further demonstrate that G-CSFstimulated migration depends on G-CSFR expression and is mediated by a mechanism that involves MMPs. These results suggest a molecular model whereby G-CSF infusion may drive, by the direct action on MSCs, HSPC egress from BM niches via synthesis and activation of MMPs. In this model, MMP-2 instead of MMP-9 is implicated, which constitutes a major difference with mouse mobilization models.

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Electrophysiological Maturation of Rat Mesenchymal Stem Cells after Induction of Vascular Smooth Muscle Cell Differentiation In Vitro

Cited by 10 publications

References 23 publications

Regeneration of Three Layers Vascular Wall by using BMP2-Treated MSC Involving HIF-1α and Id1 Expressions Through JAK/STAT Pathways

Regeneration of Three Layers Vascular Wall by using BMP2-Treated MSC Involving HIF-1α and Id1 Expressions Through JAK/STAT Pathways

Human amniotic fluid stem cell differentiation along smooth muscle lineage

Granulocyte-Colony-Stimulating Factor Stimulation of Bone Marrow Mesenchymal Stromal Cells Promotes CD34+ Cell Migration Via a Matrix Metalloproteinase-2-Dependent Mechanism

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