Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury

Strem, Brian M.; Zhu, Min; Alfonso, Zeni; Daniels, Eric; Schreiber, Ronda E.; Begyui, R.; MacLellan, W. Robb; Hedrick, Marc H.; Fraser, John K.

doi:10.1080/14653240510027226

Cited by 133 publications

(91 citation statements)

References 42 publications

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“…Spontaneous differentiation of ASCs towards cardiomyocytes has also been described (Planat-Benard et al 2004;Rangappa et al 2003;Bai et al 2007). Furthermore, in vivo animal studies, in which ASCs have been transplanted after MI, have also shown the differentiation of ASCs towards cardiomyocytes and increased cardiac function (Strem et al 2005;Zhang et al 2007). However, studies on human ASCs are limited, and only low percentages (<2%) of spontaneous differentiation have been described Song et al 2007).…”

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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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confidence: 99%

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

et al. 2008

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“…10,12,14 Our in vitro data exhibited a failure of hMADSC transdifferentiation into cardiovascular cell lineages even under a specific culture condition compared with human cardiac stem cells isolated from patients' heart biopsy sample (Supplementary Figure IV). These data suggest that the transplanted hMADSCs have significant roles as a favorable cytokine donor in ischemic myocardium and have beneficial effects on the cardiac functional recovery following MI.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a number of investigators have isolated pluripotent stem cells from adipose tissue and showed the differentiation into certain lineage cell types, including cardiovascular cells in vitro 10,[12][13][14]24 and the favorable effect on MI; 9,16-18 however, little is known regarding the interaction of transplanted donor cells and biological host tissue response, specifically, in the setting of acute MI. In this study, hMADSCs were applied to rat MI model to examine not only the therapeutic effect, but also the potential mechanism, and we have shown the favorable effect of hMADSC transplantation on cardiac functional recovery following MI characterizing the cells with a variety of pro-angiogenic cytokine and stem/progenitor chemokine expressions.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Rodriguez et al 10 have isolated multipotent adipose-derived stem cells (hMADSCs) from young human adipose tissue, and shown the differentiation capacity into not only adipose cells, but also osteoblasts, myoblasts, chondroblasts, 11 cardiomyocytes, 12 endothelial cells, 13 and smooth muscle cells 14 in vitro. Transplantation of hMADSCs into the mdx mouse, an animal model of Duchenne muscular dystrophy, resulted in substantial expression of human dystrophin in the injected muscle, 15 suggesting that hMADSCs will be an important tool for muscle cell-mediated therapy.…”

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confidence: 99%

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Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart

Masaaki

Horii

Yokoyama

et al. 2011

Laboratory Investigation

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Human multipotent adipose-derived stem cells (hMADSCs) have recently been isolated featuring extensive expansion capacity ex vivo. We tested the hypothesis that hMADSC transplantation might contribute to cardiac functional recovery by its direct or indirect effect on myocardial infarction (MI). Nude rats were either transplanted with hMADSCs or PBS (control) in ischemic myocardium immediately following MI. Echocardiographical assessment of cardiac function after MI with hMADSCs showed significant improvement of each parameter compared to that with PBS. Histological analysis also showed significantly reduced infarct size and increased capillary density in peri-infarct myocardium by hMADSC treatment. However, remarkable transdifferentiation of hMADSCs into cardiac or vascular lineage cells was not observed. Despite the less transdifferentiation capacity, hMADSCs produced robust multiple pro-angiogenic growth factors and chemokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1a (SDF-1a). Specifically, hMADSC-derived SDF-1a had a crucial role for cooperative angiogenesis, with the paracrine effect of hMADSCs and Tie2-positive bone marrow (BM) progenitor recruitment in ischemic myocardium. hMADSCs exhibit a therapeutic effect on cardiac preservation following MI, with the production of VEGF, bFGF, and SDF-1a showing paracrine effects and endogenous BM stem/progenitor recruitment to ischemic myocardium rather than its direct contribution to tissue regeneration.

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“…Similarly, cultured cells could give rise to endothelial cells whose beneficial effect has been demonstrated in vivo by their contribution to neoangiogenesis in hindlimb ischemia mice models [48] and by their ability to secrete angiogenic and antiapoptotic factors [49]. On the other hand, ADSC cardiac differentiation has been recently demonstrated when transplanted in acutely infarcted mice [50], and an improvement in the cardiac function has been proven after CD29+ SVF cell transplantation [51]. Importantly, ADSCs also induced an improvement in the cardiac function associated with an increased vasculature in an acute/reperfusion ischemia model in pig [52].…”

Section: Adipose-derived Sc (Adsc)mentioning

confidence: 99%

Stem Cells and Cardiac Disease: Where are We Going?

Pelacho

Prósper

2008

CSCR

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During the last 10 years we have witnessed the development of a new field in research termed Stem Cell Therapy. Classically, it was considered that cells had a limited division and differentiation ability; however, this dogma was challenged when new exciting results about cell multi/pluripotency were presented to the scientific community. It was found that cells from one adult tissue source were able to originate cells of a very different type. The possibility of transplanting these cells into damaged organs with the aim of substituting sick or dead tissue, triggered many studies to understand the plasticity of the stem cells and their potential in pathological situations. Nowadays, much more is understood about stem cells, although of course, many questions, especially about their mechanism of action, still need to be answered. Their benefit after transplantation has been shown experimentally and even clinically in some cases; however, the degree of stem cell contribution through their own differentiation into the transplanted tissue, has turned out to be generally low, and increasing evidence indicates that a trophic effect must play an important role in such a benefit. A better understanding of the paracrine mechanisms involved could be of great relevance in order to develop new therapies focused on stimulating endogenous cells. On the other hand, more sophisticated methods for cell transplantation combined with bio-engineering techniques have been devised in cardiac disease models. In this review we will try to provide a critical overview of the stem cell studies performed until now and to discuss some of the questions raised about the mechanisms that are involved in their putative reparative effect in cardiovascular diseases, and their origin.

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Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury

Cited by 133 publications

References 42 publications

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

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

Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart

Stem Cells and Cardiac Disease: Where are We Going?

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