Biology subjects

Nagy, M. S.

Publications and source records attributed to Nagy, M. S..

3 recordsLinked to original sources

bioRxiv2019

Human lung organoids develop into adult airway-like structures directed by physico-chemical biomaterial properties

Tissues derived from human pluripotent stem cell (hPSC) often represent early developmental time points. Yet, when transplanted into immunocompromised mice, these hPSC-derived tissues further mature, which has been enhanced with biomaterial scaffolds, gaining tissue structure and cell types similar to the native adult lung. Our goal was to define the physico-chemical biomaterial properties, including the polymer type, degradation, and pore interconnectivity of the scaffolds. Transplantation of human lung organoids (HLOs) on microporous poly(lactide-co-glycolide) (PLG) scaffolds or polycaprolactone (PCL) produced organoids that formed tube-like structures that resembled both the structure and cellular diversity of an adult lung airway. Microporous scaffolds formed from poly(ethylene glycol) (PEG) hydrogel scaffolds inhibit maturation and the HLOs remain as lung progenitors. The structures formed from cells that occupy multiple pores within the scaffold, and pore interconnectivity and polymer degradation contributed to the maturation. Finally, the overall size of the generated airway structure and the total size of the tissue was influenced by the material degradation rate. Collectively, these biomaterial platforms provide a set of tools to promote maturation of the tissues and to control the size and structure of the organoids.

bioengineering↗

bioRxiv2018

Non-adhesive alginate hydrogels support growth of pluripotent stem cell-derived intestinal organoids

Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell adhesion properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. Additionally, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.

developmental biology↗

bioRxiv2017

Bacterial Colonization Stimulates A Complex Physiological Response In The Immature Human Intestinal Epithelium

The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is diZcult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

developmental biology↗