RESUMO
OBJECTIVES: Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage. METHODS: Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents. RESULTS: Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control. CONCLUSIONS: We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.
Assuntos
Células Endoteliais/transplante , Infarto do Miocárdio/cirurgia , Neovascularização Fisiológica , Transplante de Células-Tronco , Engenharia Tecidual/métodos , Alicerces Teciduais , Função Ventricular Esquerda , Animais , Técnicas de Cultura de Células , Movimento Celular , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fibrina/metabolismo , Fibrose , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hemodinâmica , Hidrogéis , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Wistar , Fatores de Tempo , Transfecção , Pressão VentricularRESUMO
In response to the Health Physics Society's recent 'radiation safety without borders" initiative, the South Texas Chapter of the Health Physics Society selected Costa Rica as its partner country of choice. To develop an understanding of the radiation safety needs of this country, the fall 2001 University of Texas Health Science Center at Houston School of Public Health Environmental Radiation and Radioactivity class was tasked with the assignment of assessing the possible radiation safety needs and concerns for this country. The assignment culminated in a class presentation to the membership of the South Texas Chapter during its annual fall meeting. Using library and web based resources, tile students reviewed a number of public health and radiation-related topics. Life expectancies were found to be equivalent to the United States, even though significant differences in per capita health expenditures were noted. Costa Rica exhibited lower population mortality rates from major causes such as cardiovascular diseases, neoplasms, and external sources. Maternal and infant mortality rates were found to be much higher in Costa Rica than in the United States. Naturally occurring radiation sources such as uranium deposits were not identified as apparent major radiation issues of concern, although ultraviolet radiation exposures are consistently high. Several recent events in the country and the region involving patient overexposures suggest that concerns are likely focused on ensuring the proper use and maintenance of healing arts radiation equipment. The lack of available information on radioactive waste disposal suggests that waste handling also may be an issue warranting attention. The exercise proved to be very educational for the students, and the information gathered will serve to focus the Chapter's efforts when technical exchanges are initiated. The importance of linking this initiative to other existing programs within the country is also discussed.