Cardiomyogenic Potential of Human Adult Bone Marrow Mesenchymal Stem Cells <i>in Vitro</i>

Antonitsis, Polychronis; Ioannidou-Papagiannaki, Elizabeth; Kaidoglou, Aikaterini; Charokopos, Nikolaos; Kalogeridis, A.; Kouzi-Koliakou, Kokkona; Kyriakopoulou, I.; Klonizakis, Ioannis; Papakonstantinou, Christos

doi:10.1055/s-2007-989328

Cited by 51 publications

(34 citation statements)

References 22 publications

(23 reference statements)

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“…Among these various candidate cell types, MSCs have a great advantage with respect to generating functional cardiac myocytes in the infarcted myocardium because of their ease of preparation and potential to differentiate into a cardiac lineage [29,30] both in vivo and in vitro under appropriate culture conditions. In addition, the delivered MSCs have clearly improved the physiological functions of the infarcted heart by limiting infarct size and preserving at-risk regions [31,32].…”

Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

et al. 2009

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Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about three and twofold, respectively. ILK-MSCs demonstrated an increase of twofold in the ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. The adhesion rate of ILK-MSCs also had a 32.2% increase on the cardiac fibroblast-derived three-dimensional matrix and ILK-MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK-MSC transplanted rats had a 12.0% 6 3.1% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 16.0% 6 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two-thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK-MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation.

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Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

et al. 2009

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“…Bone marrow mesenchymal stem cells (MSCs) have been commonly used as donor stem cells for transplantation as they can differentiate into diverse cell types, including cardiomyocyte-like cells and vascular endothelial cells (Antonitsis et al, 2008;Yue et al, 2008). 5-Azacytidine (5-aza) is often used to induce differentiation of MSCs into myocardial cells; however, 5-aza is associated with various adverse effects as an antitumor drug (Borodovsky et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Wang

Xiaojuan

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to observe the effect of Rehmannia glutinosa oligosaccharide (RGO) on differentiation of bone marrow mesenchymal stem cells (MSCs) into cardiomyocytelike cells . Rat MSCs were isolated, treated, and grouped as follows: RGO treatment group, 5-azacytidine (5-aza) treatment group, RGO + 5-aza treatment group, and control group. Following a four-week induction period, cardiac troponin I (cTnI) levels in MSCs were quantified by chemiluminescence, and the levels of myocardial enzymes creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB) were measured using a dry chemistry analyzer. The cTnIand connexin 43 (Cx43)-positive MSC population was identified by immunofluorescence, and expression levels of cTnI and Cx43 were analyzed by western blots. Following induction, cTnI, CK, and CK-MB levels were significantly higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups (P < 0.05). In addition, fluorescence intensity of cTnI and Cx43 was higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups. No cTnI-or Cx43-positive cells were detected in the control group. Western blot analysis further confirmed that cTnI and Cx43 were not expressed in the control group, while cTnI and Cx43 was higher in the RGO + 5-aza group than in the RGO and 5-aza groups. These results suggest that MSCs can be induced by RGO to differentiate into cardiomyocyte-like cells in vitro, and that RGO in combination with 5-aza enhance differentiation of MSCs.

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“…MSCs have the potential to differentiate into cells of vascular lineages, including smooth muscle and endothelial cells. MSCs have the capacity to differentiate into cardiomyocyte-like cells in vitro (1), although it has been observed to be a rare event in in vivo studies (2,8,19,31). The effectiveness of MSC-based stem cell therapy has been attributed more to the paracrine-signaling properties of these cells, rather than to their differentiation abilities (12,30).…”

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confidence: 99%

Myocardial oxygenation and functional recovery in infarct rat hearts transplanted with mesenchymal stem cells

Chacko¹,

Khan²,

Kuppusamy³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Stem cell therapy for myocardial tissue repair is limited by the poor survival of transplanted cells, possibly because of inadequate supply of oxygen and nutrients. The purpose of this study was to assess the oxygenation level and functional recovery after allogenic transplantation of mesenchymal stem cells (MSC) in a rat model of myocardial infarction (MI). Myocardial oxygen tension (Po(2)) was measured by electron paramagnetic resonance oximetry using an implantable oxygen-sensing spin probe (OxySpin). MSCs incubated with OxySpins showed substantial uptake of the probe without affecting its oxygen sensitivity or calibration. The cells internalized with OxySpins were able to differentiate into osteogenic, adipogenic, cardiomyocyte, and endothelial cell lineages. The labeled cells tested positive for CD44 and CD29 markers and negative for the hematopoietic markers CD14 and CD45. For the in vivo studies, MI was induced in rats by permanently ligating the left anterior descending coronary artery. MSCs with OxySpins were transplanted in the infarct region of hearts. A significant increase in Po(2) was observed in the MSC group compared with the untreated MI group (18.1 +/- 2.6 vs. 13.0 +/- 1.8 mmHg, n = 4, P < 0.05) at 4 wk after transplantation. Echocardiography showed a significant improvement in ejection fraction and fraction shortening, which inversely correlated with the magnitude of fibrosis in the treated hearts. The cell-transplanted hearts also showed an increase in vascular endothelial growth factor level and capillary density in the infarct region. The study established our ability to measure and correlate changes in myocardial tissue oxygenation with cardiac function in infarcted rat hearts treated with MSCs.

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Cardiomyogenic Potential of Human Adult Bone Marrow Mesenchymal Stem Cells in Vitro

Abstract: These results indicate that adult human bone marrow mesenchymal stem cells treated with 5-aza can differentiate towards a cardiomyogenic lineage IN VITRO.

Cited by 51 publications

References 22 publications

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Myocardial oxygenation and functional recovery in infarct rat hearts transplanted with mesenchymal stem cells

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