Enhanced Cell Therapy for Ischemic Heart Disease

Bonaros, Nikolaos; Rauf, Rauend; Schachner, Thomas; Laufer, Günther; Kocher, Alfred

doi:10.1097/tp.0b013e3181880f9e

Cited by 30 publications

(18 citation statements)

References 83 publications

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“…To avoid these drawbacks, several studies have attempted to inoculate EPCs directly at sites of vascular repair and healing, including infracted areas of the heart. Compared to systemic injection, this approach led to significantly greater, but still marginal, numbers of injected cells that survive in the infarct area and eventually contribute to tissue regeneration [114]. To overcome these limitations of conventional transplantation methods, there has been intense development of scaffolds that promote in situ cell retention and avoid non-specific cell homing.…”

Section: Reviewmentioning

confidence: 99%

Endothelial progenitor cells and integrins: adhesive needs

Caiado

Dias

2012

Fibrogenesis Tissue Repair

112

105

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In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of this cell population as a relevant clinical agent.

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Section: Reviewmentioning

confidence: 99%

Endothelial progenitor cells and integrins: adhesive needs

Caiado

Dias

2012

Fibrogenesis Tissue Repair

112

105

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“…In relation to (2)–(4), several efforts, such as coculture with EC and the investigation of numbers of layered cell sheets, are performed as described in this paper. In addition, several possibilities to enhance the therapeutic effects of engineered tissue grafts for cardiac disease are discussed in many laboratories including ours [61, 62]. Although the myocardial tissue engineering including scaffold-free cell sheet-based tissue engineering stands at its start line, the technology is thought to have promising and enormous possibilities.…”

Section: Future Possibilities Of Myocardial Tissue Engineeringmentioning

confidence: 99%

Regenerative Therapies Using Cell Sheet-Based Tissue Engineering for Cardiac Disease

Haraguchi

Shimizu

Yamato

et al. 2011

Cardiology Research and Practice

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At present, cardiac diseases are a major cause of morbidity and mortality in the world. Recently, a cell-based regenerative medicine has appeared as one of the most potential and promising therapies for improving cardiac diseases. As a new generational cell-based regenerative therapy, tissue engineering is focused. Our laboratory has originally developed cell sheet-based scaffold-free tissue engineering. Three-dimensional myocardial tissue fabricated by stacking cardiomyocyte sheets, which are tightly interconnected to each other through gap junctions, beats simultaneously and macroscopically and shows the characteristic structures of native heart tissue. Cell sheet-based therapy cures the damaged heart function of animal models and is clinically applied. Cell sheet-based tissue engineering has a promising and enormous potential in myocardial tissue regenerative medicine and will cure many patients suffering from severe cardiac disease. This paper summarizes cell sheet-based tissue engineering and its satisfactory therapeutic effects on cardiac disease.

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“…It is now evident that an extremely limited percentage of stem cells will engraft and survive within the recipient myocardium following intracoronary infusion or transendocardial injection (17). Moreover, the use of injectable scaffolds to augment stem cell engraftment is not devoid of harmful decrease in myocardial perfusion.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Mixed Esters of Butyric and Retinoic Acid Affording Myocardial Survival and Repair without Stem Cell Transplantation

Lionetti

Cantoni

Cavallini

et al. 2010

Journal of Biological Chemistry

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Possible cardiac repair by adult stem cell transplantation is currently hampered by poor cell viability and delivery efficiency, uncertain differentiating fate in vivo, the needs of ex vivo cell expansion, and consequent delay in transplantation after the onset of heart attack. By the aid of magnetic resonance imaging, positron emission tomography, and immunohistochemistry, we show that injection of a hyaluronan mixed ester of butyric and retinoic acid (HBR) into infarcted rat hearts afforded substantial cardiovascular repair and recovery of myocardial performance. HBR restored cardiac [18F]fluorodeoxyglucose uptake and increased capillary density and led to the recruitment of endogenous Stro-1-positive stem cells. A terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay demonstrated that HBR-treated hearts exhibited a decrease in the number of apoptotic cardiomyocytes. In isolated rat cardiomyocytes and Stro-1 stem cells, HBR enhanced the transcription of vascular endothelial growth factor, hepatocyte growth factor, kdr, akt, and pim-1. HBR also increased the secretion of vascular endothelial growth factor and hepatocyte growth factor, suggesting that the mixed ester may have recruited both myocardial and Stro-1 cells also. An increase in capillarogenesis was induced in vitro with medium obtained from HBR-exposed cells. In the infarcted myocardium, HBR injection increased histone H4 acetylation significantly. Acetyl-H4 immunoreactivity increased in rat cardiomyocytes and Stro-1 cells exposed to HBR, compared with untreated cells. In conclusion, efficient cardiac regenerative therapy can be afforded by HBR without the need of stem cell transplantation or vector-mediated gene delivery.

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Enhanced Cell Therapy for Ischemic Heart Disease

Cited by 30 publications

References 83 publications

Endothelial progenitor cells and integrins: adhesive needs

Endothelial progenitor cells and integrins: adhesive needs

Regenerative Therapies Using Cell Sheet-Based Tissue Engineering for Cardiac Disease

Hyaluronan Mixed Esters of Butyric and Retinoic Acid Affording Myocardial Survival and Repair without Stem Cell Transplantation

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