Cardiomyogenic differentiation of human bone marrow mesenchymal cells: Role of cardiac extract from neonatal rat cardiomyocytes

Labovsky, Vivian; Hofer, Erica Leonor; Feldman, L.; Vallone, Valeria Fernández; Rivello, Hernán Garcı́a; Bayés‐Genís, Antoni; Insúa, Andrés Hernando; Levìn, Mariano J.; Chasseing, Norma Alejandra

doi:10.1016/j.diff.2009.10.001

Cited by 42 publications

(32 citation statements)

References 35 publications

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“…A small percentage of hMSCs engrafted into the myocardium in a mouse model of myocardial infarction showed de novo expression of cardiomyogenic proteins like desmin, b-myosin heavy chain, a-actinin, cardiac troponin T, and phospholamban like the host cardiomyocytes, and sarcomeric organization of the contractile proteins was observed [38]. Recent studies on hBM-MSCs reported on cardiomyogenic differentiation in vitro [39][40][41][42]. However, hBM-MSCs co-cultured with neonatal rat cardiomyocytes displayed limited cardiomyogenic plasticity [43], and treatment with 5-azacytidine caused despite the absence of differentiation of hMSCs into cardiomyocytes, profound changes in current density [44].…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Siegel¹,

Krause²,

Wöhrle³

et al. 2012

Stem Cells and Development

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Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC-mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1 + mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Siegel¹,

Krause²,

Wöhrle³

et al. 2012

Stem Cells and Development

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“…Finally, incubation with 5-AZA, a treatment reported to induce differentiation of mesenchymal progenitor cells toward a cardiogenic lineage (28,30), failed to induce any electrophysiological change in CD34 ϩ cells. These data, in agreement with the previously reported lack of upregulation of human cardiac genes in CD34 ϩ cells during coculture (36), rule against a paracrine effect or a nuclear reprogramming process, induced by soluble factors deriving from the coculture conditions.…”

Section: Discussionmentioning

confidence: 90%

“…Finally, in Previous studies reported that cell incubation with DNA demethylating agents, such as 5-AZA, is able to induce a cardiogenic program in various cell types (28,30). We, therefore, incubated CD34 ϩ cells with this drug for 24 h (see METHODS for details), followed by culture for 6 days in a drug-free medium.…”

Section: Electrophysiological Features Of Cd34mentioning

confidence: 99%

Human cord blood CD34⁺ progenitor cells acquire functional cardiac properties through a cell fusion process

Avitabile

Crespi

Brioschi

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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The efficacy of cardiac repair by stem cell administration relies on a successful functional integration of injected cells into the host myocardium. Safety concerns have been raised about the possibility that stem cells may induce foci of arrhythmia in the ischemic myocardium. In a previous work ( 36 ), we showed that human cord blood CD34+ cells, when cocultured on neonatal mouse cardiomyocytes, exhibit excitation-contraction coupling features similar to those of cardiomyocytes, even though no human genes were upregulated. The aims of the present work are to investigate whether human CD34+ cells, isolated after 1 wk of coculture with neonatal ventricular myocytes, possess molecular and functional properties of cardiomyocytes and to discriminate, using a reporter gene system, whether cardiac differentiation derives from a (trans)differentiation or a cell fusion process. Umbilical cord blood CD34+ cells were isolated by a magnetic cell sorting method, transduced with a lentiviral vector carrying the enhanced green fluorescent protein (EGFP) gene, and seeded onto primary cultures of spontaneously beating rat neonatal cardiomyocytes. Cocultured EGFP+/CD34+-derived cells were analyzed for their electrophysiological features at different time points. After 1 wk in coculture, EGFP+ cells, in contact with cardiomyocytes, were spontaneously contracting and had a maximum diastolic potential (MDP) of −53.1 mV, while those that remained isolated from the surrounding myocytes did not contract and had a depolarized resting potential of −11.4 mV. Cells were then resuspended and cultured at low density to identify EGFP+ progenitor cell derivatives. Under these conditions, we observed single EGFP+ beating cells that had acquired an hyperpolarization-activated current typical of neonatal cardiomyocytes (EGFP+ cells, −2.24 ± 0.89 pA/pF; myocytes, −1.99 ± 0.63 pA/pF, at −125 mV). To discriminate between cell autonomous differentiation and fusion, EGFP+/CD34+ cells were cocultured with cardiac myocytes infected with a red fluorescence protein-lentiviral vector; under these conditions we found that 100% of EGFP+ cells were also red fluorescent protein positive, suggesting cell fusion as the mechanism by which cardiac functional features are acquired.

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“…We therefore hypothesized that the use of bone marrow derived mesenchymal stem cells might be a better option. Mesenchymal stem cells have been extensively studied for their cardiac reparability and regenerative potential Kim et al 2010.;Labovsky et al 2010;Haider et al 2009) besides having superior transgene carrying capability Huang et al 2010;Tang et al 2010;Haider et al 2008). Besides, we also opted to replace Vegf with survival signaling molecule Akt to support survival of the genetically modified mesenchymal stem cells (Jiang et al 2006).…”

Section: Combining Stem Cell Transplantation and Angiopoietin-1 Deliverymentioning

confidence: 99%

Angiopoietin-1 for Myocardial Angiogenesis

Lai¹,

Afzal²,

Ashraf³

et al. 2011

Myocarditis

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Cardiomyogenic differentiation of human bone marrow mesenchymal cells: Role of cardiac extract from neonatal rat cardiomyocytes

Cited by 42 publications

References 35 publications

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Human cord blood CD34⁺ progenitor cells acquire functional cardiac properties through a cell fusion process

Angiopoietin-1 for Myocardial Angiogenesis

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Cardiomyogenic differentiation of human bone marrow mesenchymal cells: Role of cardiac extract from neonatal rat cardiomyocytes

Cited by 42 publications

References 35 publications

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process

Angiopoietin-1 for Myocardial Angiogenesis

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Product

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Human cord blood CD34⁺ progenitor cells acquire functional cardiac properties through a cell fusion process