You Can’t Judge a Book by Its Cover

Menasché, Philippe

doi:10.1161/circulationaha.105.610287

Cited by 11 publications

(9 citation statements)

References 20 publications

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“…Using videomicroscopy we also found several double labeled, double nuclei cells indicative of cell fusion. However, cell fusion showed high variations among different culture and detection techniques, and therefore extensive cell fusion as an in vitro artefact cannot be ruled out [14,34,35]. During our investigations we only observed a few unquestionable cell fusions which cannot account for the rescue of the high number of damaged cardiomyoblasts [36].…”

Section: Discussionmentioning

confidence: 95%

“…One plausible mechanism for the rescuing effect is that transplanted cells improve regeneration through secreting paracrine factors [14,28-31]. However, results from our experiments with the plate insert show that paracrine factors secreted by the cells are probably too low in our system to have any beneficial effect on these severely damaged cells.…”

Section: Discussionmentioning

confidence: 95%

“…On the other hand, several studies have found that co-culture of cardiomyocytes with pluripotent stem cells resulted in transdifferentiation of these cells into cardiomyocytes, which raised the hope that in vitro cultured tissue blocks can later be used for cardiac repair [12,13]. However, although it is possible to construct a tissue in vitro this does not mean that its building blocks will perform similarly when implanted in vivo [14]. Indeed, recent investigations found difficult to reproduce transdifferentiation and that bone marrow derived cells generate cardiomyocytes not by transdifferentiation but rather through cell fusion [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections

et al. 2010

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Background: Bone marrow derived mesenchymal stem cells (MSCs) are promising candidates for cell based therapies in myocardial infarction. However, the exact underlying cellular mechanisms are still not fully understood. Our aim was to explore the possible role of direct cell-to-cell interaction between ischemic H9c2 cardiomyoblasts and normal MSCs. Using an in vitro ischemia model of 150 minutes of oxygen glucose deprivation we investigated cell viability and cell interactions with confocal microscopy and flow cytometry.Results: Our model revealed that adding normal MSCs to the ischemic cell population significantly decreased the ratio of dead H9c2 cells (H9c2 only: 0.85 ± 0.086 vs. H9c2+MSCs: 0.16 ± 0.035). This effect was dependent on direct cell-tocell contact since co-cultivation with MSCs cultured in cell inserts did not exert the same beneficial effect (ratio of dead H9c2 cells: 0.90 ± 0.055). Confocal microscopy revealed that cardiomyoblasts and MSCs frequently formed 200-500 nm wide intercellular connections and cell fusion rarely occurred between these cells. Conclusion:Based on these results we hypothesize that mesenchymal stem cells may reduce the number of dead cardiomyoblasts after ischemic damage via direct cell-to-cell interactions and intercellular tubular connections may play an important role in these processes.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections

et al. 2010

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“…In 2001, the concept was introduced that HSC could transdifferentiate into cardiomyocytes, resulting in substantial de novo myocardium formation after myocardial infarction [3]. Since different animal studies yielded discrepant results [4–8], the ability of bone marrow-derived cells to differentiate into cardiac cell types remains subject of controversy [9]. Nonetheless, in the majority of studies, HSC injection was associated with improvements in cardiac function and attenuation of post-infarct remodeling.…”

Section: Cell Types Used For the Treatment Of Myocardial Ischemiamentioning

confidence: 99%

Bone Marrow Cell Injection for Chronic Myocardial Ischemia: The Past and the Future

Ramshorst

Rodrigo

Schalij

et al. 2011

J. of Cardiovasc. Trans. Res.

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Intramyocardial bone marrow cell injection is currently being investigated as a new therapeutic option for the treatment of chronic myocardial ischemia. Experimental studies and early phase clinical trials established a favorable safety profile of this approach and suggested that bone marrow cell injection was associated with clinical and functional improvements. Recently, a randomized, double-blind, placebo-controlled trial demonstrated that intramyocardial bone marrow cell injection was associated with beneficial effects on myocardial perfusion and anginal symptoms. However, the mechanisms by which bone marrow cells may improve myocardial perfusion are only partially understood, and several issues remain to be addressed. This review aims to provide a summary of the current experience with bone marrow cell therapy as a novel treatment option for patients with chronic myocardial ischemia. Therefore, the most frequently used cell types will be reviewed along with the mechanisms through which bone marrow cells may improve myocardial perfusion and function. In addition, possible routes of delivery are compared, and the results of currently available experimental and clinical studies are discussed.

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“…The possibility of cell fusion in our model was addressed in our first publication and its frequency was found to be extremely low [40]. However, it must be noted that the extent of cell fusion shows extremely high variation among different culture and detection techniques, and it cannot be ruled out that extensive cell fusion is an in vitro artifact [28, 52, 53]. Still, recent studies suggest that despite the low frequency cell fusion may exert relevant impact on stem cell programming or reprogramming in the heart [54].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Direct Effects of Human Adipose- and Bone-Marrow-Derived Stem Cells on Postischemic Cardiomyoblasts in anIn VitroSimulated Ischemia-Reperfusion Model

Szepes

Benkő

Cselenyák

et al. 2013

Stem Cells International

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Regenerative therapies hold a promising and exciting future for the cure of yet untreatable diseases, and mesenchymal stem cells are in the forefront of this approach. However, the relative efficacy and the mechanism of action of different types of mesenchymal stem cells are still incompletely understood. We aimed to evaluate the effects of human adipose- (hASC) and bone-marrow-derived stem cells (hBMSCs) and adipose-derived stem cell conditioned media (ACM) on the viability of cardiomyoblasts in an in vitro ischemia-reperfusion (I-R) model. Flow cytometric viability analysis revealed that both cell treatments led to similarly increased percentages of living cells, while treatment with ACM did not (I-R model: 12.13 ± 0.75%; hASC: 24.66 ± 2.49%; hBMSC: 25.41 ± 1.99%; ACM: 13.94 ± 1.44%). Metabolic activity measurement (I-R model: 0.065 ± 0.033; hASC: 0.652 ± 0.089; hBMSC: 0.607 ± 0.059; ACM: 0.225 ± 0.013; arbitrary units) and lactate dehydrogenase assay (I-R model: 0.225 ± 0.006; hASC: 0.148 ± 0.005; hBMSC: 0.146 ± 0.004; ACM: 0.208 ± 0.009; arbitrary units) confirmed the flow cytometric results while also indicated a slight beneficial effect of ACM. Our results highlight that mesenchymal stem cells have the same efficacy when used directly on postischemic cells, and differences found between them in preclinical and clinical investigations are rather related to other possible causes such as their immunomodulatory or angiogenic properties.

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You Can’t Judge a Book by Its Cover

Cited by 11 publications

References 20 publications

Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections

Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections

Bone Marrow Cell Injection for Chronic Myocardial Ischemia: The Past and the Future

Comparison of the Direct Effects of Human Adipose- and Bone-Marrow-Derived Stem Cells on Postischemic Cardiomyoblasts in anIn VitroSimulated Ischemia-Reperfusion Model

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