



@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 {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 {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 {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.}
}
