Biology subjects

Lopez-Sandoval, R.

Publications and source records attributed to Lopez-Sandoval, R..

3 recordsLinked to original sources

bioRxiv2025

Integrated Microfluidic Platform for High-Throughput Generation of Intestinal Organoids in Hydrogel Droplets

Organoid research offers valuable insights into human biology and disease, but reproducibility and scalability remain significant challenges, particularly for epithelial organoids. Here, we present an integrated microfluidic platform that addresses these limitations by enabling high-throughput generation of uniform hydrogel microparticles embedded with intestinal stem cells. Our platform includes a cell distribution system for homogenous cell encapsulation and a microfluidic oil removal module for efficient particle transfer to aqueous media. We demonstrate the successful culture and differentiation of both healthy and tumor-derived intestinal organoids within these microparticles, achieving high homogeneity and reproducibility. This integrated microfluidic approach holds promise for scalable and standardized organoid production, with potential applications in drug screening, disease modeling, and personalized medicine.

bioengineering↗

bioRxiv2025

Modeling host-microbe interactions in immunocompetent engineered human gut tissues

The intestinal mucosal barrier contains microbial organisms within the lumen while preserving the ability to absorb nutrients. Dietary, microbial, and other exposures shaped human barrier evolution and continue to impact disease susceptibility. Here, we established engineered barrier models of the human small intestine and colon composed of a multilineage epithelium, mucus layer, accessible microbial compartment and autologous tissue-resident immune cells. The epithelium has crypt- and villus-like topological domains, with stem cells differentiating into absorptive and secretory lineages with region-specific identities. Secreted mucins accumulate apically, forming a dense mucus layer separating the epithelium from colonizing commensal and pathogenic bacteria. Intestinal memory T cells integrate into and interact with the epithelium. We use the engineered intestinal tissues to identify an epithelial gene regulatory network underlying response to Salmonella Typhimurium infection, and uncover epithelial-immune-pathogen crosstalk coordinating cytokine release and epithelial damage. Overall, this work allows for the modular integration of epithelial, microbial, and immune compartments providing a versatile system for studying human intestinal physiology and pathologies.

bioengineering↗

bioRxiv2025

High-throughput histopathology for complex in vitro models

Human complex in vitro models (CIVMs) have demonstrated remarkable potential to study tissue development, physiology and disease at high-throughput. To effectively employ these miniaturized systems in translational preclinical research, their in-depth benchmarking is pivotal. Histology has been the core of tissue characterization for centuries and the foundation of spatial phenotyping. However, standard histology workflows are inherently low-throughput and centered on large tissue pieces. This does not match the high sample volumes and small sample sizes in CIVM research. Here, we introduce a holistic histo-workflow, utilizing 3D-printed histomolds that facilitate co-planar embedding of CIVMs at high-throughput, resulting in up to 48 samples in one section. We developed a variety of model-specific histomold designs that enable spatially controlled histological sectioning and downstream analyses. We describe these workflows, including mold generation, highplex staining and image analysis, and exemplify their application to histological analyses of various CIVMs. Altogether, the histomolds introduced here afford opportunities for CIVM processing and analysis, while significantly reducing labor and reagent resources, thereby democratizing high-throughput CIVM in histopathology.

pathology↗