Tesis
Permanent URI for this communityhttps://hdl.handle.net/11285/345119
Colección de Tesis y Trabajos de grado (informe final del proyecto de investigación, tesina, u otro trabajo académico diferente a Tesis, sujeto a la revisión y aceptación de una comisión dictaminadora) presentados por alumnos para obtener un grado académico del Tecnológico de Monterrey.
Para enviar tu trabajo académico al RITEC, puedes consultar este Infográfico con los pasos generales para que tu tesis sea depositada en el RITEC.
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- 3D printed tumor on chips for the culture and maturation of heterotypic cancer spheroids as a platform for drug testing(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2022-12-05) Gallegos Martínez, Salvador; GALLEGOS MARTINEZ, SALVADOR; 814051; puemcuervo, emipsanchez; Shrike Zhang, Yu; Gonzáles Meljem, José Mario; Luna Aguirre, Claudia Maribel; Olvera Posadas, Daniel; School of Engineering and Sciences; Campus Monterrey; Trujillo de Santiago, GrisselThe recapitulation of cancer environment in tumor-on-chip systems will greatly contribute to accelerate cancer studies in the fronts on fundamental research, pharmacological testing of new therapeutic compounds, and personalized medicine. Here we describe the development of two microfluidic platforms aimed to contribute to the advance of tumor-on-chip research. First, we describe a simple and robust method for the fabrication, maturation, and extended culture of large heterotypic cancer (MCF7 and MCF7/fibroblasts) spheroids (~900 µm in diameter) in a 3D-printed mini continuous stirred tank reactor (mini-CSTR). In brief, MCF7 and MCF7/BJ cell suspensions (5×104 cells) were incubated in batch culture to form discoid cell aggregates (600 µm in diameter). These microtissues were then transferred into the mini-CSTR and continuously fed with culture media for an extended time (~30 days). The spheroids progressively increased in size during the first 20 days of perfusion culture to reach a steady diameter. We characterized the spheroid morphology, architecture and the evolution of expression of relevant tumor-related genes (i.e., ER, VEGF, Ki67, Bcl2, LDHA, and HIF-1α) in spheroids cultured for 30 days. This mini-CSTR culture strategy enables the simple and reproducible fabrication of relatively large spheroids and offers great potential for studying the effects of diverse effectors on tumor progression. In addition, we introduce a 3D-printed microfluidic system that can be generically used to culture tumor-tissues under well-controlled environments. The system is composed by three compartments. The left and right compartments have two inlets and two outlets which provide means to continuously feed liquid streams to the system. The central compartment is designed to host a hydrogel where a microtissue can be confined and cultured. A transparent lid can be adapted to enable visual inspection under a microscope. We conducted fluorescent and FITC dextran tracer experiments to characterize the hydraulic performance of the system. In addition, we cultured MCF7 and MCF7/BJ spheroids embedded in a GelMA hydrogel constructs (placed in the central chamber), to illustrate the use of this system to sustain long term micro-tissue culture experiments. We also present experimental results that illustrate the flexibility and robustness of this 3D-printed device for tumor-on-chip experiments including pharmacological testing of anticancer compounds. These “open-source” organ-on-chip systems are intended to be a general-purpose resource to facilitate and democratize the development of tumor-on-chip applications. We also explored the use of these cell aggregates and some of the characterization techniques to develop educational activities in the context of tissue engineering. Students fabricated a DIY (do it yourself) incubator and cultured spheroids for 7 days on average. They evaluated glucose consumption, size progression and change in color of the culture media. In this proposed activity students were exposed to concepts and basic experimental duties commonly use in a tissue engineering lab.
- Research and development of emerging technologies for exosome-based cancer diagnostics and therapeutics(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2023-06-12) Ayala Mar, Sergio Antonio; AYALA MAR, SERGIO ANTONIO; 850524; puemcuervo, emipsanchez; Benavides Lozano, Jorge Alejandro; Zavala Arcos, Judith; Hernández Pérez, Jesús; School of Engineering and Sciences; Campus Monterrey; Alsberg, EbenExosomes hold the potential to transform cancer nanomedicine. As cellular nanoparticles, exosomes shuttle biomolecules between cells and tissues, providing a unique platform for diagnosis and targeted therapy. The study of exosomes and their potential applications has gained significant attention, and a vast body of literature illustrates the potential of exosomes to improve cancer care. However, the clinical translation of exosome-based diagnostics and therapeutics faces several challenges. Limitations in exosome research include a lack of standardized protocols for exosome isolation, characterization, and functional analysis. Concerns about their efficacy and safety arise primarily from their biodistribution in vivo. Additionally, our understanding of their biology remains limited. Emerging technologies, particularly those capable of manipulating complex biological systems at the nanoscale, are proposed to overcome these limitations. Such technologies could potentially accelerate the development of novel therapeutic strategies in personalized and precision medicine through exosome-based products. Nevertheless, extensive proof of concept in multiple preclinical models is required to ensure clinical efficacy and to advance the translation of exosome-based products from bench to clinic. In this work, we present a multidisciplinary approach to address the challenges encountered in exosome isolation, therapeutic delivery, and functional analysis. We designed a microfluidic device based on dielectrophoresis for rapid, size-based exosome separation. For targeted delivery, we encapsulated exosomes in photocrosslinkable and biodegradable alginate hydrogels. To better understand exosome biology, we developed a 3D cell culture model and studied the effect of an inhibitor of exosome release on the expression and subcellular localization of molecular targets for cancer therapeutics.