Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551014
Pertenecen a esta colección Tesis y Trabajos de grado de los Doctorados correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Engineering scalable exosome isolation platforms and biomimetic scaffolds for ADSC-based regenerative therapies(2025-06-12) Torres Bautista, Abril Lorena; González Valdes, José; Torres Acosta, Mario A.; Romero Robles, Laura E.; Aguilar Jiménez, Oscar A.; Benavides Lozano, Jorge A.; Sawadkar, PrasadThe therapeutic use of exosomes, small extracellular vesicles involved in paracrine signaling and intercellular communication, has emerged as a promising alternative to cell-based therapies in regenerative medicine. However, their clinical application remains limited by challenges in scalable production, efficient purification, and functional validation in biologically relevant models. This dissertation addresses these limitations by integrating bioprocess optimization with engineered human-based platforms for tissue regeneration. The experimental work presented in this thesis is divided into two main parts. The first part explores strategies for the scalable and selective isolation of exosomes from mammalian cell cultures. This included the design and optimization of aqueous two-phase systems (ATPS) for the purification of CaCo2-derived exosomes, which achieved high recovery efficiency (>80%) with minimal protein contamination. A comprehensive review of emerging technologies such as microfluidics, membranebased methods, and bioreactor platforms was also conducted and classified according to their scalability and purity output. The second part investigates the regenerative and immunomodulatory potential of ADSC and their exosomes using advanced biomimetic systems. A human in vitro burn wound model was developed to assess the impact of ADSC-derived exosomes on macrophage modulation and angiogenesis, resulting in enhanced vascularization and the immunomodulatory regulation of IL-6 and IL-10 expression. In parallel, a set of tunable ternary scaffolds composed of collagen, elastin, and fibrin were developed to support adipose tissue regeneration both in vitro and in vivo. The scaffolds enhanced the adipogenic differentiation of ADSCs without external induction, as confirmed by the upregulation of adipogenic marker such as CEBPα, PPARγ, FABP4 and Caveolin-1. By combining scalable manufacturing strategies with functional evaluation in biomimetic systems, this dissertation contributes to the development of next-generation platforms for exosome-based regenerative therapies. The findings presented here offer new insights into the engineering of both bioprocesses and bioactive scaffolds, supporting future applications in personalized medicine and soft tissue repair
- Exosome-like vesicles in intercellular communication: Investigating the role of exosomal proteins in the pathophysiology of obesity and exploring the potential therapeutic use of exosomes.(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2023-06-15) Donoso Quezada, Javier Alejandro; GONZALEZ VALDEZ, JOSE GUILLERMO; 234501; González Valdez, José Guillermo; puemcuervo, emipsanchez; Ramos Parra, Perla Azucena; Genevieve Brunck, Marion Emilie; Chávez Santoscoy, Rocío Alejandra; Gómez Loredo, Alma Elizabeth; Escuela de Ingeniería y Ciencias; Campus Monterrey; Brix Pedersen, SusanneType 2 diabetes mellitus (T2DM) is a chronic condition characterized by impaired insulin sensitivity, resulting in hyperglycemia, dyslipidemia, and other metabolic changes that can damage organs and tissues over time. Obesity is the primary risk factor for the development of T2DM, as it triggers chronic inflammation in adipose tissue, leading to the secretion of adipokines that reduce insulin sensitivity in peripheral tissues. On their part, exosomes, small extracellular vesicles that cells use for intercellular communication, are critical players in fundamental biological processes such as cell growth, metabolism, and inflammation. Changes in the production or composition of exosomes can lead to health issues. In this dissertation, we explore the role of exosomes in cell-to-cell communication and their potential therapeutic use, focusing on the proteomic alterations that occur in exosomes during obesity and their potential functional consequences. The experimental work in this dissertation is divided into three parts. First, we studied the effect of hyperglycemia on cell function in adipocytic and hepatocytic cell lines. Second, we investigated the changes in exosome proteome resulting from obesity and physical training in a mouse model of diet- induced obesity, emphasizing the functional implications of these alterations. Finally, we evaluated the potential therapeutic use of exosomes to deliver bioactive compounds in vitro. This work aims to enhance our understanding of exosome biology and its relevance to health and disease, particularly metabolic disorders such as obesity and T2DM. By shedding light on the functional consequences of altered exosome proteome and exploring the potential of exosomes for therapeutic purposes, this dissertation provides important insights that may pave the way for novel therapeutic approaches for metabolic disorders.
- 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.