Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes

Rangappa, Sunil; Chen, Fen; Lee, Eng Hin; Bongso, Ariff; Wei, Eugene Sim Kwang

doi:10.1016/s0003-4975(02)04568-x

Cited by 321 publications

(259 citation statements)

References 22 publications

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“…This prevents methylation of DNA after cell division thereby reactivating transcription of genes previously silenced. 5-Azacytidine was repeatedly reported to induce differentiation of various selected adult stem cell populations into cardiomyocytes [9,40,45,46].…”

Section: Mechanism Of Action Of 5-azacytidinementioning

confidence: 99%

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

et al. 2006

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Previously, mouse bone marrow-derived stem cells (MSC) treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was to investigate the efficiency of a similar differentiation strategy in human mononuclear cells obtained from healthy bone marrow donors. After 1-3 passages, cultures were exposed for 24 h to 5-azacytidine (3 µM) followed by 6 weeks of further culture. Drug treatment did not induce expression of myogenic marker MyoD or cardiac markers Nkx2.5 and GATA-4 and did not yield beating cells during follow-up. In patch clamp experiments, approximately 10-15% of treated and untreated cells exhibited L-type Ca 2+ currents. Almost all cells showed outwardly rectifying K + currents of rapid or slow activation kinetics. Mean current amplitude at +60 mV doubled after 6 weeks of treatment compared with time-matched controls. Membrane capacitance of treated cells was significantly larger than in controls 2 weeks after treatment and remained high after 6 weeks. Expression levels of mRNAs for the K + channels Kv1.1, Kv1.5, Kv2.1, Kv4.3 and KCNMA1 and for the Ca 2+ channel Ca v 1.2 were not affected by 5-azacytidine. Treatment with potassium channel blockers tetraethylammonium and clofilium at concentrations shown previously to inhibit rapid or slowly activating K + currents of hMSC inhibited proliferation of these cells. Our results suggest that despite the absence of differentiation of hMSC into cardiomyocytes, treatment with 5-azacytidine caused profound changes in current density.Cell Research (2006) 16:949-960.

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Section: Mechanism Of Action Of 5-azacytidinementioning

confidence: 99%

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

et al. 2006

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“…Co-culturing BMMSCs with CMCs induced BMMSCs to differentiate into CMCs. 17,18 BMMSCs 3 and ADSCs 18 treated with 5-azacytidine were induced to express CMC phenotype characteristics. Transforming growth factor-b1 (TGF-b1) and TGF-b2 stimulated cardiomyogenic differentiation of BMMSCs 2 and embryonic stem cells 19 in vitro, respectively.…”

Section: Introductionmentioning

confidence: 99%

In vitro cardiomyogenic differentiation of adipose‐derived stromal cells using transforming growth factor‐β1

Gwak

Bhang

Yang

et al. 2009

Cell Biochemistry & Function

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Transplanting stem cells differentiated towards a cardiac lineage can regenerate cardiac muscle tissues to treat myocardial infarction. In this study, we tested the hypothesis that transforming growth factor-b1 (TGF-b1) induces cardiomyogenic differentiation of adiposederived stromal cells (ADSCs) in vitro. Rat ADSCs were cultured with TGF-b1 (10 ng ml À1 ) for 2 weeks in vitro. ADSCs cultured without TGF-b1 served as a control. The mRNA expression of cardiac-specific gene was induced by TGF-b1, while the control culture did not show cardiac-specific gene expression. Immunocytochemical analyses showed that a small fraction of ADSCs cultured with TGF-b1 for 2 weeks stained positively for cardiac myosin heavy chain (MHC) and a-sarcomeric actin. Flow cytometric analyses showed that the proportion of cells expressing cardiac MHC increased with TGF-b1. However, no mesenchymal differentiation (e.g., osteogenic and adipogenic differentiation) was detected other than cardiomyogenic differentiation. These results showed that TGF-b1 induce ADSC cardiomyogenic differentiation in vitro, which could be useful for myocardial infarction stem cell therapy.

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“…A potential source of stem cells for transplantation is adipose tissue. Adipose-tissue-derived stem cells (ASCs) are of mesenchymal origin, can easily be harvested in large quantities, show high proliferation rates in culture and have the capacity to differentiate towards several cell types, including cardiomyocytes (Rangappa et al 2003;Oedayrajsingh-Varma et al 2006).…”

mentioning

confidence: 99%

Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin

et al. 2008

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Adipose-derived stem cells (ASCs) are promising candidates for therapy in myocardial infarction (MI). However, the frequency of human ASCs that differentiate towards cardiomyocytes is low. We hypothesized that adherence to extracellular matrix molecules that are upregulated after MI might increase human stem cell differentiation towards cardiomyocytes. We analysed putative ASC differentiation on fibronectin-coated, laminincoated and uncoated culture plates. Expression of cardiac markers in cells was analysed 1, 3 and 5 weeks after stimulation with 5-aza-2-deoxycytidine. After 1 week, mRNA expression of myosin light chain-2α (MLC-2α), an early marker in cardiomyocyte development, was increased significantly in treated cells, independent of coating. At 5 weeks, however, mRNA expression of the late cardiomyocyte development marker SERCA2α was only significantly increased in 5-aza-2-deoxycytidine-treated cells cultured on laminin. Significantly higher numbers of cells were immunopositive for MLC-2α in cultures of treated cells grown on laminin-coated wells, when compared with cultures of treated cells grown on uncoated wells, both at 1 week and at 5 weeks. Furthermore, after 3 weeks, significantly more α-actinin-and desmin-positive cells were detected after treatment with 5-aza-2-deoxycytidine, but only in uncoated wells. After 5 weeks, however, the number of desmin-positive cells was only significantly increased after treatment of cells with 5-aza-2-deoxycytidine and culture on laminin (61% positive cells). Thus, we have found that a high percentage of human ASCs can be differentiated towards cardiomyocytes; this effect can be improved by laminin, especially during late differentiation.

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Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes

Cited by 321 publications

References 22 publications

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

In vitro cardiomyogenic differentiation of adipose‐derived stromal cells using transforming growth factor‐β1

Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin

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