



@article {3284,
	title = {Building and repairing the heart: What can we learn from embryonic development?},
	journal = {BioMed Research International},
	volume = {2014},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	abstract = {Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed. {\textcopyright} 2014 Ana G. Freire et al.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84900022530\&partnerID=40\&md5=892677562f6828017ad5a18fe9e97e83},
	author = {Freire, AG and Resende, TP and Pinto-Do-{\'O}, P.}
}
@article {3303,
	title = {Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure},
	journal = {ACS Nano},
	volume = {8},
	year = {2014},
	note = {Cited By (since 1996):4Export Date: 21 November 2014},
	month = {2014},
	pages = {2033 - 2047},
	abstract = {Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design. {\textcopyright} 2014 American Chemical Society.},
	keywords = {adult cardiac progenitor cell, cardiac differentiation, mechano- transduction, substrate nanotopography, YAP/TAZ},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84896911335\&partnerID=40\&md5=c15ea687a167227f6d91e71dcc812590},
	author = {Mosqueira, D. and Pagliari, S. and Uto, K and Ebara, M and Romanazzo, S. and Escobedo-Lucea, C and Nakanishi, J and Taniguchi, A and Franzese, O and Di Nardo, P. and Goumans, MJ and Traversa, E and Pinto-Do-{\'O}, P. and Aoyagi, T. and Forte, G.}
}
@article {3305,
	title = {Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms},
	journal = {Stem Cell Research and Therapy},
	volume = {5},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	abstract = {Introduction. Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. However, whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). Herein we report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play. Methods. Human umbilical cord tissue-derived MSCs (UCX{\textregistered}), obtained by using a proprietary technology developed by ECBio, were delivered via intramyocardial injection to C57BL/6 females subjected to permanent ligation of the left descending coronary artery. Moreover, medium produced by cultured UCX{\textregistered} preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays. Results: Evaluation of the effects upon intramyocardial transplantation shows that UCX{\textregistered} preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX{\textregistered} further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX{\textregistered}-conditioned medium displayed (a) proangiogenic activity by promoting the formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs), and (b) antiapoptotic activity in HL-1 cardiomyocytes subjected to hypoxia. Moreover, in adult murine cardiac Sca- 1{\textsection}ssup{\textsection}+{\textsection}esup{\textsection} progenitor cells (CPCs), conditioned medium enhanced mitogenic activity while activating a gene program characteristic of cardiomyogenic differentiation. Conclusions: UCX{\textregistered} preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX{\textregistered} were attributed to paracrine mechanisms that appear to enhance angiogenesis, limit the extent of the apoptosis, augment proliferation, and activate a pool of resident CPCs. Overall, these results suggest that UCX{\textregistered} should be considered an alternative cell source when designing new therapeutic approaches to treat MI. {\textcopyright} 2014 Nascimento et al.; licensee BioMed Central Ltd.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84896713037\&partnerID=40\&md5=22fdca81d834ec78c8196552c3d250ae},
	author = {Nascimento, D.S. and Mosqueira, D. and Sousa, L.M. and Teixeira, M. and Filipe, M. and Resende, TP and Ara{\'u}jo, A.F. and Valente, M. and Almeida, J. and Martins, J.P. and Santos, J.M. and B{\'a}rcia, R.N. and Cruz, P. and Cruz, H. and Pinto-Do-{\'O}, P.}
}
@article {3301,
	title = {Primary bone marrow mesenchymal stromal cells rescue the axonal phenotype of twitcher mice},
	journal = {Cell Transplantation},
	volume = {23},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {239 - 252},
	abstract = {Krabbe{\textquoteright}s disease (KD) is a demyelinating disorder caused by the deficiency of lysosomal galactocerebrosidase (GALC), affecting both the central (CNS) and the peripheral nervous system (PNS). A current therapy, hematopoietic stem cell transplantation (HSCT), is ineffective at correcting the PNS pathology. We have previously shown that systemic delivery of immortalized bone marrow-derived murine mesenchymal stromal cells (BM-MSCs) diminishes the neuropathology of transplanted Twitcher mice, a murine model of KD. In this study, to move one step closer to clinical application, the effectiveness of a systematic delivery of primary BM-MSCs to promote recovery of the Twitcher PNS was assessed. Primary BM-MSCs grafted to the Twitcher sciatic nerve led to increased GALC activity that was not correlated to decreased psychosine (the toxic GALC substrate) accumulation. Nevertheless, BM-MSC transplantation rescued the axonal phenotype of Twitcher mice in the sciatic nerve, with an increased density of both myelinated and unmyelinated axons in transplanted animals. Whereas no increase in myelination was observed, upon transplantation an increased proliferation of Schwann cell precursors occurred. Supporting these findings, in vitro, BM-MSCs promoted neurite outgrowth of Twitcher sensory neurons and proliferation of Twitcher Schwann cells. Moreover, BM-MSCs expressed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and promoted increased BDNF synthesis by neighboring Schwann cells. Besides their action in neurons and glia, BM-MSCs led to macrophage activation in Twitcher sciatic nerves. In summary, primary BM-MSCs diminish the neuropathology of Twitcher sciatic nerves by coordinately affecting neurons, glia, and macrophages. {\textcopyright} 2014 Cognizant Comm. Corp.},
	keywords = {Axonal degeneration, Bone marrow-derived mesenchymal stromal cells (BM-MSCs), Krabbe{\textquoteright}s disease (KD), Twitcher mice},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84893339069\&partnerID=40\&md5=51c17895a58b06f3b302616459dff62b},
	author = {Miranda, C.O. and Teixeira, C.A. and Sousa, V.F. and Santos,TE and Liz, M.A. and Marques,AM and Pinto-Do-{\'O}, P. and Sousa, M.M.}
}
@article {3326,
	title = {Sca-1+cardiac progenitor cells and heart-making: A critical synopsis},
	journal = {Stem Cells and Development},
	volume = {23},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {2263 - 2273},
	abstract = {The identification, in the adult, of cardiomyocyte turnover events and of cardiac progenitor cells (CPCs) has revolutionized the field of cardiovascular medicine. However, the low rate of CPCs differentiation events reported both in vitro and in vivo, even after injury, raised concerns on the biological significance of these subsets. In this Comprehensive Review, we discuss the current understanding of cardiac Lin-Sca-1+cells in light of what is also known for cellular compartments with similar phenotypes in other organs. The Lin-Sca-1+heart subset is heterogeneous and displays a mesenchymal profile, characterized by a limited ability to generate cardiomyocytes in vitro and in vivo, even after injury. There is no evidence for Sca-1 expression in embryonic cardiovascular progenitors. In other organs, Sca-1 expression is mainly observed on mesoderm-derived cells, although it is not restricted to stem/progenitor cell populations. It is urgent to determine, at a single cell level, to which extent cardiac Lin-Sca-1+cells overlap with the fibroblast compartment.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84907432293\&partnerID=40\&md5=f861431ef4750c567f4dff89b4bc013c},
	author = {Valente, M. and Nascimento, D.S. and Cumano, A. and Pinto-Do-{\'O}, P.}
}
@article {3283,
	title = {Stable phenotype and function of immortalized Lin-Sca-1 + cardiac progenitor cells in long-term culture: A step closer to standardization},
	journal = {Stem Cells and Development},
	volume = {23},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {1012 - 1026},
	abstract = {Putative cardiac progenitor cells (CPCs) have been identified in the myocardium and are regarded as promising candidates for cardiac cell-based therapies. Although two distinct populations of CPCs reached the clinical setting, more detailed studies are required to portray the optimal cell type and therapeutic setting to drive robust cell engraftment and cardiomyogenesis after injury. Owing to the scarcity of the CPCs and the need for reproducibility, the generation of faithful cellular models would facilitate this scrutiny. Here, we evaluate whether immortalized Lin-Sca-1+ CPCs (iCPC Sca-1) represent their native-cell counterpart, thereby constituting a robust in vitro model system for standardized investigation in the cardiac field. iCPCSca-1 were established in vitro as plastic adherent cells endowed with robust self-renewal capacity while preserving a stable phenotype in long-term culture. iCPCSca-1 differentiated into cardiomyocytic-, endothelial-, and smooth muscle-like cells when subjected to appropriate stimuli. The cell line consistently displayed features of Lin -Sca-1+ CPCs in vitro, as well as in vivo after intramyocardial delivery in the onset of myocardial infarction (MI). Transplanted iCPCSca-1 significantly attenuated the functional and anatomical alterations caused by MI while promoting neovascularization. iCPCSca-1 are further shown to engraft, establish functional connections, and differentiate in loco into cardiomyocyte- and vasculature-like cells. These data validate iCPCSca-1 as an in vitro model system for Lin-Sca-1+ progenitors and for systematic dissection of mechanisms underlying CPC subsets engraftment/differentiation in vivo. Moreover, iCPCSca-1 can be regarded as a ready-to-use CPCs source for pre-clinical bioengineering studies toward the development of novel strategies for restoration of the damaged myocardium. {\textcopyright} Copyright 2014, Mary Ann Liebert, Inc. 2014.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84896901797\&partnerID=40\&md5=35b7014573b8734d5c21f2089cdc038d},
	author = {Freire, AG and Nascimento, D.S. and Forte, G. and Valente, M. and Resende, TP and Pagliari, S. and Abreu, C and Carvalho, I and Nardo, P.D. and Pinto-Do-{\'O}, P.}
}
@article {2849,
	title = {Adult stem cells and biocompatible scaffolds as smart drug delivery tools for cardiac tissue repair},
	journal = {Current Medicinal Chemistry},
	volume = {20},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {3429 - 3447},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883267656\&partnerID=40\&md5=b03789229cfac322e56bb69b4fc644ea},
	author = {Pagliari, S. and Romanazzo, S. and Mosqueira, D. and Pinto-Do-{\'O}, P. and Aoyagi, T. and Forte, G.}
}
@article {2900,
	title = {Stable phenotype and function of immortalized Lin-Sca-1+ cardiac progenitor cells in long-term culture: a step closer to standardization.},
	journal = {Stem Cells Dev},
	volume = {Epub ahead of print},
	year = {2013},
	month = {12-2013},
	isbn = {PMID: 24367889 },
	url = {http://www.ncbi.nlm.nih.gov/pubmed/24367889},
	author = {Freire, AG and Nascimento, D.S. and Forte, G. and Valente, M. and Resende, TP and Pagliari, S. and Abreu, C and Carvalho, I and Di Nardo, P. and Pinto-Do-{\'O}, P.}
}
@conference {2192,
	title = {Automatic myocardial infarction size extraction in an experimental murine model using an anatomical model},
	booktitle = {Proceedings - International Symposium on Biomedical ImagingIEEE Comput. Soc. Conf. Comput. Vis. Pattern Recogn.},
	series = {2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012},
	year = {2012},
	note = {Conference code: 91746Export Date: 21 November 2012Source: ScopusArt. No.: 6235546doi: 10.1109/ISBI.2012.6235546Language of Original Document: EnglishCorrespondence Address: Esteves, T.; Departamento de Engenharia Electrot{\'e}cnica e de Computadores, Faculdade de Engenharia, Universidade Do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, PortugalReferences: Degabriele, N., Griesenbach, U., Sato, K., Critical appraisal of the mouse model of myocardial infarction (2004) Experimental Physiology, 89 (4), pp. 497-505;Lutgens, E., Daemen, M., Muinck, E., Chronic myocardial infarction in the mouse: Cardiac structural and functional changes (1998) Cardiovascular Research, 41, pp. 586-593; 
Takagawa, J., Zhang, Y., Wong, M., Myocardial infarct size measurement in the mouse chronic infarction model: Comparison of area- and length-based approaches (2007) Journal of Applied Physiology, 102, pp. 2104-2111; 
Nascimento, D., Valente, M., Esteves, T., Pina, M.F., Guedes, J.G., Freire, A., Quelhas, P., Pinto-Do, O.P., Miquant - Semi-automation of infarct size assessment in models of cardiac ischemic injury (2011) Plos One, 6 (9), pp. 1-8; 
Esteves, T., Valente, M., Nascimento, D., Pinto-Do, O.P., Quelhas, P., Automatic and semi-automatic analysis of the extension of myocardial infarction in an experimental murine model (2011) Proceedings of IbPRIA, LNCS, 6669, pp. 151-158; 
Pfeffer, M., Pfeffer, J., Fishbein, M., Myocardial infarct size and ventricular function in rats (1979) Circulation Research, 44, pp. 503-512
Sponsors: The Institute of Electrical and Electronic Engineers; Engineering in Medicine and Biology Society; Signal Processing Society},
	month = {2012///},
	pages = {310 - 313},
	address = {Barcelona},
	abstract = {Experimental rodent models of induced ischemic injury have been extensively used in biomedical research to study molecular, cellular and histological alterations following myocar-dial infarction. These models are increasingly employed to assess the potential of newly developed therapies for functional restoration of the damaged heart. Such studies are based on myocardial infarction induction followed by different therapeutic interventions and subsequent analysis of the infarct size. This analysis is used to evaluate the extent to which such interventions meet recovery of the lost myocardial tissue. Infarct size is defined as the percentage of the left ventricle affected by coronary artery occlusion. The infarct size is traditionally estimated manually delineating the infarcted and normal tissue areas in the left ventricle of the excised heart. However, this is a time-consuming, arduous and prone to bias process. Herein, we developed an anatomic model, adapted through expectation maximization, which allows for fully automatic analysis of the data. Experimental validation is performed comparing the proposed approach with manual annotation. The results obtained through anatomical model adaptation were coherent with those manually obtained and the differences where never higher than 10\%. {\textcopyright} 2012 IEEE.},
	keywords = {Anatomic models, anatomical model, Anatomical models, Automatic analysis, Biomedical research, Coronary arteries, expectation maximization, Experimental validations, Image segmentation, Infarct size, Ischemic injuries, Left ventricles, Manual annotation, Maximum principle, Medical imaging, Murine model, Myocardial Infarction, Myocardial infarction size, Myocardial tissue, Normal tissue, Rodent models, Therapeutic intervention, Tissue},
	isbn = {19457928 (ISSN); 9781457718588 (ISBN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84864832695\&partnerID=40\&md5=087bcb09e5d5319029623283cba34c34},
	author = {Esteves, T. and Valente, M. and Nascimento, D.S. and Pinto-Do-{\'O}, P. and Quelhas, P.}
}
@conference {2817,
	title = {Automatic myocardial infarction size extraction in an experimental murine model using an anatomical model},
	booktitle = {Proceedings - International Symposium on Biomedical Imaging},
	year = {2012},
	note = {Export Date: 2 October 2013Source: ScopusArt. No.: 6235546},
	month = {2012///},
	pages = {310 - 313},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84864832695\&partnerID=40\&md5=6716e8eb5d812d3e0ffe54d87369d746},
	author = {Esteves, T. and Valente, M. and Nascimento, D.S. and Pinto-Do-{\'O}, P. and Quelhas, P.}
}
@book {2224,
	title = {Automatic and semi-automatic analysis of the extension of myocardial infarction in an experimental murine model},
	series = {Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)Lect. Notes Comput. Sci.},
	volume = {6669 LNCS},
	year = {2011},
	note = {Conference code: 85429Cited By (since 1996): 1Export Date: 21 November 2012Source: Scopusdoi: 10.1007/978-3-642-21257-4_19Language of Original Document: EnglishCorrespondence Address: Esteves, T.; Departamento de Engenharia Electrot{\'e}cnica e de Computadores, Faculdade de Engenharia, Universidade Do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; email: meb09026@fe.up.ptReferences: Degabriele, N., Griesenbach, U., Sato, K., Critical appraisal of the mouse model of myocardial infarction (2004) Experimental Physiology, 89 (4), pp. 497-505;Takagawa, J., Zhang, Y., Wong, M., Myocardial infarct size measurement in the mouse chronic infarction model: Comparison of area- and length-based approaches (2007) Journal of Applied Physiology, 102, pp. 2104-2111; 
Alattar, M., Osman, N., Fahmy, A., Myocardial segmentation using constrained multi-seeded region growing (2010) LNCS, 6112, pp. 89-98. , Campilho, A., Kamel, M. (eds.) ICIAR 2010 Springer, Heidelberg; 
Wu, Q., Merchant, F., Castleman, K., (1996) Microscope Image Processing, , ch. 7. Elsevier, Amsterdam; 
Gonzalez, R., Woods, R., Eddins, S., (2004) Digital Image Processing Using MATLAB, , ch. 9. Pearson Education, London; 
Sharma, N., Aggarwal, L., Automated medical image segmentation techniques (2010) Journal of Medical Physics, 35 (1), pp. 3-14; 
Pham, D., Xu, C., A survey of current methods in medical image segmentation (1998) Annual Review of Biomedical Engineering, 2, pp. 315-338; 
Hamarneh, G., Li, X., Watershed segmentation using prior shape and appearance knowledge (2009) Image and Vision Comp, 27 (1-2), pp. 59-68; 
Khadir, S., Ahamed, R., Moving toward region-based image segmentation techniques: A study (2009) Journal of Theoretical and Applied Information Technology, 5 (1), pp. 1-7; 
Ahmed, M., Mohamad, D., Segmentation of brain mr images for tumor extraction by combining kmeans clustering and perona-malik anisotropic diffusion model (2010) International Journal of Image Processing, 2 (1), pp. 1-8; 
Mayer, A., Greenspan, H., An adaptive mean-shift framework for MRI brain segmentation (2009) IEEE Trans. on Medical Imaging, 28 (8), pp. 1-12; 
Dabov, K., Foi, A., Katkovnik, V., Image denoising by sparse 3d transform-domain collaborative filtering (2007) IEEE Trans. on Image Processing, 16 (8), pp. 1-16; 
Otsu, N., A threshold selection method from gray level histograms (1979) IEEE Trans. Systems, Man and Cybernetics, 9 (1), pp. 62-66; 
Marcuzzo, M., Quelhas, P., Campilho, A., Mendon{\c c}a, A.M., Campilho, A., Automated arabidopsis plant root cell segmentation based on svm classification and region merging (2009) Computers in Biology and Medicine, 39 (9), pp. 1-9; 
Bleau, A., Leon, J., Watershed-based segmentation and region merging (2000) Computer Vision and Image Understanding, 77 (3), pp. 317-370
},
	month = {2011///},
	pages = {151 - 158},
	address = {Las Palmas de Gran Canaria},
	abstract = {Rodent models of myocardial infarction (MI) have been extensively used in biomedical research towards the implementation of novel regenerative therapies. Permanent ligation of the left anterior descending (LAD) coronary artery is a commonly used method for inducing MI both in rat and mouse. Post-mortem evaluation of the heart, particularly the MI extension assessment performed on histological sections, is a critical parameter for this experimental setting. MI extension, which is defined as the percentage of the left ventricle affected by the coronary occlusion, has to be estimated by identifying the infarcted- and the normal-tissue in each section. However, because it is a manual procedure it is time-consuming, arduous and prone to bias. Herein, we introduce semi-automatic and automatic approaches to perform segmentation which is then used to obtain the infarct extension measurement. Experimental validation is performed comparing the proposed approaches with manual annotation and a total error not exceeding 8\% is reported in all cases. {\textcopyright} 2011 Springer-Verlag.},
	keywords = {Extension evaluations, Image analysis, Image segmentation, Infarct extension evaluation, k-means, Mammals, meanshift, otsu, Pattern recognition, region growing, Tissue, watershed},
	isbn = {03029743 (ISSN); 9783642212567 (ISBN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79959927807\&partnerID=40\&md5=360bb21a8c1c3a5fdd394c647fcadbbc},
	author = {Esteves, T. and Valente, M. and Nascimento, D.S. and Pinto-Do-{\'O}, P. and Quelhas, P.}
}
@book {2818,
	title = {Automatic and semi-automatic analysis of the extension of myocardial infarction in an experimental murine model},
	series = {Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)},
	volume = {6669 LNCS},
	year = {2011},
	note = {Cited By (since 1996):1Export Date: 2 October 2013Source: Scopus},
	month = {2011///},
	pages = {151 - 158},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79959927807\&partnerID=40\&md5=58726bd7fc58cf587a13af9e3ba0c151},
	author = {Esteves, T. and Valente, M. and Nascimento, D.S. and Pinto-Do-{\'O}, P. and Quelhas, P.}
}
@article {2234,
	title = {Bone marrow-derived endothelial progenitors expressing delta-like 4 (Dll4) regulate tumor angiogenesis},
	journal = {PLoS ONEPLoS ONE},
	volume = {6},
	year = {2011},
	note = {Cited By (since 1996): 8Export Date: 21 November 2012Source: ScopusArt. No.: e18323doi: 10.1371/journal.pone.0018323Language of Original Document: EnglishCorrespondence Address: Dias, S.; Angiogenesis Laboratory, CIPM/Portuguese Institute of Oncology, Lisbon, Portugal; email: sergidias@ipolisboa.min-saude.ptChemicals/CAS: fibronectin, 86088-83-7; vasculotropin, 127464-60-2; DLL4 protein, mouse; Intracellular Signaling Peptides and Proteins; Membrane ProteinsReferences: Asahara, T., Masuda, H., Takahashi, T., Kalka, C., Pastore, C., Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization (1999) Circ Res, 85, pp. 221-228;Rafii, S., Lyden, D., Benezra, R., Hattori, K., Heissig, B., Vascular and haematopoietic stem cells: Novel targets for anti-angiogenesis therapy? (2002) Nat Rev Cancer, 2, pp. 826-835. , Review; 
Lyden, D., Hattori, K., Dias, S., Costa, C., Blaikie, P., Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth (2001) Nat Med, 7, pp. 1194-1201; 
Larrivee, B., Niessen, K., Pollet, I., Corbel, S.Y., Long, M., Minimal contribution of marrow-derived endothelial precursors to tumor vasculature (2005) J Immunol, 175, pp. 2890-2899; 
Peters, B.A., Diaz, L.A., Polyak, K., Meszler, L., Romans, K., Contribution of bone marrow-derived endothelial cells to human tumor vasculature (2005) Nat Med, 11, pp. 261-262; 
Pasquier, E., Dias, S., Endothelial progenitor cells: Hope beyond controversy (2010) Curr Cancer Drug Targets, 10 (8), pp. 914-921; 
Dudley, A.C., Udagawa, T., Melero-Martin, J.M., Shih, S.C., Curatolo, A., Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors (2010) Blood, 116 (17), pp. 2267-2271; 
Krebs, L.T., Xue, Y., Norton, C.R., Shutter, J.R., Maguire, M., Notch signaling is essential for vascular morphogenesis in mice (2000) Genes Dev, 14, pp. 1343-1352; 
Uyttendaele, H., Ho, J., Rossant, J., Kitajewski, J., Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium (2001) Proc Natl Acad Sci U S A, 98, pp. 5643-5648; 
Duarte, A., Hirashima, M., Benedito, R., Trindade, A., Diniz, P., Dosage-sensitive requirement for mouse Dll4 in artery development (2004) Genes Dev, 18, pp. 2474-2478; 
Gale, N.W., Dominguez, M.G., Noguera, I., Pan, L., Hughes, V., Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development (2004) Proc Natl Acad Sci U S A, 101, pp. 15949-15954; 
Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele (1996) Nature, 380, pp. 435-439; 
Mailhos, C., Modlich, U., Lewis, J., Harris, A., Bicknell, R., Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis (2001) Differentiation, 69, pp. 135-144; 
Oliner, J., Min, H., Leal, J., Yu, D., Rao, S., Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2 (2004) Cancer Cell, 6, pp. 507-516; 
Patel, N.S., Li, J.L., Generali, D., Poulsom, R., Cranston, D.W., Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function (2005) Cancer Res, 65, pp. 8690-8697; 
Williams, C.K., Li, J.L., Murga, M., Harris, A.L., Tosato, G., Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function (2006) Blood, 107, pp. 931-939; 
Caiado, F., Real, C., Carvalho, T., Dias, S., Notch pathway modulation on bone marrow-derived vascular precursor cells regulates their angiogenic and wound healing potential (2008) PLoS One, 3, pp. e3752; 
Escudier, B., Eisen, T., Stadler, W.M., Szczylik, C., Oudard, S., Sorafenib in advanced clear-cell renal-cell carcinoma (2007) N Engl J Med, 356, pp. 125-134; 
Llovet, J.M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Sorafenib in advanced hepatocellular carcinoma (2008) N Engl J Med, 359, pp. 378-390; 
Motzer, R.J., Bukowski, R.M., Targeted therapy for metastatic renal cell carcinoma (2006) J Clin Oncol, 24, pp. 5601-5608; 
Bergers, G., Hanahan, D., Modes of resistance to anti-angiogenic therapy (2008) Nat Rev Cancer, 8, pp. 592-603; 
Verheul, H.M., Pinedo, H.M., Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition (2007) Nat Rev Cancer, 7, pp. 475-485; 
Noguera-Troise, I., Daly, C., Papadopoulos, N.J., Coetzee, S., Boland, P., Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis (2006) Nature, 444, pp. 1032-1037; 
Ridgway, J., Zhang, G., Wu, Y., Stawicki, S., Liang, W.C., Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis (2006) Nature, 444, pp. 1083-1087; 
Moore, M.A., Hattori, K., Heissig, B., Shieh, J.H., Dias, S., Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1 (2001) Ann N Y Acad Sci, 938, pp. 36-45. , discussion 45-37; 
Yamaguchi, J., Kusano, K.F., Masuo, O., Kawamoto, A., Silver, M., Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization (2003) Circulation, 107, pp. 1322-1328; 
Leslie, J.D., Ariza-McNaughton, L., Bermange, A.L., McAdow, R., Johnson, S.L., Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis (2007) Development, 134, pp. 839-844; 
Trindade, A., Kumar, S.R., Scehnet, J.S., Lopes-da-Costa, L., Becker, J., Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos (2008) Blood, 112, pp. 1720-1729; 
Huang, M.T., Mason, J.C., Birdsey, G.M., Amsellem, V., Gerwin, N., Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis (2005) Blood, 106, pp. 1636-1643; 
Deutsch, U., Schlaeger, T.M., Dehouck, B., Doring, A., Tauber, S., Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice (2008) Exp Cell Res, 314, pp. 1202-1216; 
Dias, S., Thomas, H., Balkwill, F., Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model (1998) Int J Cancer, 75 (1), pp. 151-157; 
Scott, K.A., Holdsworth, H., Balkwill, F.R., Dias, S., Exploiting changes in the tumour microenvironment with sequential cytokine and matrix metalloprotease inhibitor treatment in a murine breast cancer model (2000) Br J Cancer, 83 (11), pp. 1538-1543
},
	month = {2011///},
	abstract = {Neo-blood vessel growth (angiogenesis), which may involve the activation of pre-existing endothelial cells (EC) and/or the recruitment of bone marrow-derived vascular precursor cells (BM-VPC), is essential for tumor growth. Molecularly, besides the well established roles for Vascular endothelial growth factor (VEGF), recent findings show the Notch signalling pathway, in particular the ligand Delta-like 4 (Dll4), is also essential for adequate tumor angiogenesis; Dll4 inhibition results in impaired, non-functional, angiogenesis and reduced tumor growth. However, the role of BM-VPC in the setting of Notch pathway modulation was not addressed and is the subject of the present report. Here we show that SDF-1 and VEGF, which are produced by tumors, increase Dll4 expression on recruited BM-VPC. Mechanistically, BM-VPC activated, in a Dll4-dependent manner, a transcriptional program on mature EC suggestive of EC activation and stabilization. BM-VPC induced ICAM-2 and Fibronectin expression on EC, an effect that was blocked by a Dll4-specific neutralizing antibody. In vivo, transplantation of BM-VPC with decreased Dll4 into tumor-bearing mice resulted in the formation of microvessels with decreased pericyte coverage and reduced fibronectin expression. Consequently, transplantation of BM-VPC with decreased Dll4 resulted in impaired tumor angiogenesis, increased tumor hypoxia and apoptosis, and decreased tumor growth. Taken together, our data suggests that Dll4 expression by BM-VPC affects their communication with tumor vessel endothelial cells, thereby modulating tumor angiogenesis by affecting vascular stability. {\textcopyright} 2011 Real et al.},
	keywords = {angiogenesis, animal, animal cell, animal tissue, Animals, apoptosis, article, blood vessel, Blood Vessels, bone marrow, bone marrow cell, Bone Marrow Cells, cell activation, Cell Line, Tumor, cell proliferation, controlled study, cytology, delta like 4 protein, DLL4 protein, mouse, Endothelial Cells, endothelium cell, Female, Fibronectin, gene expression, gene expression regulation, genetics, human, human cell, Humans, hypoxia, in vitro study, in vivo study, intercellular adhesion molecule 2, Intracellular Signaling Peptides and Proteins, membrane protein, Membrane Proteins, metabolism, Mice, mouse, Mus, neoplasm, Neoplasms, neovascularization (pathology), Neovascularization, Pathologic, neutralizing antibody, nonhuman, Notch receptor, Pathology, pericyte, protein expression, signal peptide, solid tumor, stem cell, stem cell transplantation, Stem cells, stromal cell derived factor 1, tumor cell line, tumor growth, unclassified drug, vascularization, vasculotropin},
	isbn = {19326203 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79953685607\&partnerID=40\&md5=60a33b7d91c1502050bc560303255881},
	author = {Real, C. and Rem{\'e}dio, L. and Caiado, F. and Igreja, C. and Borges, C. and Trindade, A. and Pinto-Do-{\'O}, P. and Yagita, H. and Duarte, A. and Dias, S.}
}
@article {2815,
	title = {MIQuant - semi-automation of infarct size assessment in models of cardiac ischemic injury},
	journal = {PLoS ONE},
	volume = {6},
	year = {2011},
	note = {Cited By (since 1996):1Export Date: 2 October 2013Source: ScopusArt. No.: e25045},
	month = {2011///},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-80053583980\&partnerID=40\&md5=757f7f25dcffa46f5fd66ccee74f13f0},
	author = {Nascimento, D.S. and Valente, M. and Esteves, T. and De F{\'a}tima De Pina, M. and Guedes, J.G. and Freire, A. and Quelhas, P. and Pinto-Do-{\'O}, P.}
}
@article {2816,
	title = {Systemic delivery of bone marrow-derived mesenchymal stromal cells diminishes neuropathology in a mouse model of Krabbe{\textquoteright}s disease},
	journal = {Stem Cells},
	volume = {29},
	year = {2011},
	note = {Cited By (since 1996):4Export Date: 2 October 2013Source: Scopus},
	month = {2011///},
	pages = {1738 - 1751},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-80054957115\&partnerID=40\&md5=460f6b3c9735980171039cf772450e6f},
	author = {Miranda, C.O. and Teixeira, C.A. and Liz, M.A. and Sousa, V.F. and Franquinho, F. and Forte, G. and Di Nardo, P. and Pinto-Do-{\'O}, P. and Sousa, M.M.}
}
@article {2285,
	title = {TNF-α regulates the effects of irradiation in the mouse bone marrow microenvironment},
	journal = {PLoS ONEPLoS ONE},
	volume = {5},
	year = {2010},
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Padmanabhan, A., Baker, J.A., Zirpoli, G., Sait, S.N., Ford, L.A., Acute myeloid leukemia and myelodysplastic syndrome following breast cancer: Increased frequency of other cancers and of cancers in multiple family members (2008) Leuk Res, 32 (12), pp. 1820-1823; 
Zhang, Y., Harada, A., Bluethmann, H., Wang, J.B., Nakao, S., Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: Increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro (1995) Blood, 86 (8), pp. 2930-2937; 
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Drutskaya, M.S., Ortiz, M., Liepinsh, D.J., Kuprash, D.V., Nedospasov, S.A., Inhibitory effects of tumor necrosis factor on hematopoiesis seen in vitro are translated to increased numbers of both committed and multipotent progenitors in TNF-deficient mice (2005) Exp Hematol, 33 (11), pp. 1348-1356; 
R{\"u}be, C.E., Wilfert, F., Uthe, D., Schmid, K.W., Knoop, R., Modulation of radiation-induced tumour necrosis factor alpha (TNF-alpha) expression in the lung tissue by pentoxifylline (2002) Radiother Oncol, 64 (2), pp. 177-187; 
Zhang, M., Qian, J., Xing, X., Kong, F.M., Zhao, L., Inhibition of the tumor necrosis factor-alpha pathway is radioprotective for the lung (2008) Clin Cancer Res, 14 (6), pp. 1868-1876; 
Daigle, J.L., Hong, J.H., Chiang, C.S., McBride, W.H., The role of tumor necrosis factor signaling pathways in the response of murine brain to irradiation (2001) Cancer Res, 61 (24), pp. 8859-8865; 
Dy, L.C., Pei, Y., Travers, J.B., Augmentation of ultraviolet B radiation-induced tumor necrosis factor production by the epidermal platelet-activating factor receptor (1999) J Biol Chem, 274 (38), pp. 26917-26921; 
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Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, et al. (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 31:109(5): 625-37.35Natoli G, Costanzo A, Guido F, Moretti F, Bernardo A, et al. (1998) Nuclear factor kB-independent cytoprotective pathways originating at tumor necrosis factor receptor-associated factor 2. J Biol Chem 273(47): 31262-72.36Barkett, M., Gilmore, T.D., Control of apoptosis by Rel/NF-kappaB transcription factors (1999) Oncogene, 18 (49), pp. 6910-6924; 
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Raza, A., Qawi, H., Lisak, L., Andric, T., Dar, S., Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone (2000) Blood, 95 (5), pp. 1580-1587
},
	month = {2010///},
	abstract = {Background: Secondary bone marrow (BM) myelodysplastic syndromes (MDS) are increasingly common, as a result of radio or chemotherapy administered to a majority of cancer patients. Patients with secondary MDS have increased BM cell apoptosis, which results in BM dysfunction (cytopenias), and an increased risk of developing fatal acute leukemias. In the present study we asked whether TNF-α, known to regulate cell apoptosis, could modulate the onset of secondary MDS. Principal Findings:We show that TNF-α is induced by irradiation and regulates BM cells apoptosis in vitro and in vivo. In contrast to irradiated wild type (WT) mice, TNF-α deficient (TNF-α KO) mice or WT mice treated with a TNF-α-neutralizing antibody were partially protected from the apoptotic effects of irradiation. Next we established a 3-cycle irradiation protocol, in which mice were sub-lethally irradiated once monthly over a 3 month period. In this model, irradiated WT mice presented loss of microsatellite markers on BM cells, low white blood cell (WBC) counts, reduced megakaryocyte (MK) and platelet levels (thrombocytopenia) and macrocytic anemia, phenoypes that suggest the irradiation protocol resulted in BM dysfunction with clinical features of MDS. In contrast, TNF-α KO mice were protected from the irradiation effects: BM cell apoptosis following irradiation was significantly reduced, concomitant with sustained BM MK numbers and absence of other cytopenias. Moreover, irradiated WT mice with long term (>=5 months) BM dysfunction had increased BM angiogenesis, MMPs and VEGF and NFkB p65, suggestive of disease progression. Conclusion:Taken together, our data shows that TNF-α induction following irradiation modulates BM cell apoptosis and is a crucial event in BM dysfunction, secondary MDS onset and progression. {\textcopyright} 2010 Cacha{\c c}o et al.},
	keywords = {angiogenesis, animal, animal cell, animal experiment, animal model, animal tissue, Animals, Antibodies, Neutralizing, apoptosis, article, Blood, blood cell count, Blotting, Western, bone marrow, bone marrow cell, Bone Marrow Cells, C57BL mouse, Cell Line, clinical feature, controlled study, cytokine production, disease course, drug effect, Enzyme Activation, flow cytometry, genetics, immunology, in vitro study, in vivo study, irradiation, leukocyte, leukocyte count, Leukocytes, macrocytic anemia, male, matrix metalloproteinase, Matrix Metalloproteinases, megakaryocyte, Megakaryocytes, metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, microenvironment, microsatellite marker, mouse, mouse mutant, Mus, myelodysplastic syndrome, neovascularization (pathology), Neovascularization, Pathologic, neutralizing antibody, nonhuman, Pathology, phenotype, protein expression, radiation dose, radiation exposure, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription polymerase chain reaction, thrombocytopenia, transcription factor RelA, tumor necrosis factor alpha, tumor necrosis factor alpha antibody, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, vascularization, vasculotropin, vasculotropin A, Western blotting, zymography},
	isbn = {19326203 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77749280454\&partnerID=40\&md5=741f4070ed47c15899f89c6d21b4e8f8},
	author = {Cacha{\c c}o, A.S. and Carvalho, T. and Santos, A.C. and Igreja, C. and Fragoso, R. and Rio, C.O. and Ferreira, M. and Serpa, J. and Correia, S. and Pinto-Do-{\'O}, P. and Dias, S.}
}
