Bioengeneered 3D human intestine: use of silk "scaffolds" in studies of Giardia lamblia-host interaction

• Grant number: 19/02918-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2019
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Renata Rosito Tonelli
• Grantee: Renata Rosito Tonelli
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The genus Giardia include diplomonadida parasites of global importance that causes diarrhea in humans (Giardia lamblia specie) and other vertebrates. In vitro two-dimensional (2D) cell cultures for studying Giardia infections that have physiological relevance are rare and the use of animal models are limited to ethical constraints. For these reasons, 2D cell monolayers are been replaced by three-dimensional (3D) models that offer many advantages such as the maintenance of tissue structure and the cell types found in the host environment. Three-dimensional human intestinal model can be set up in the lab using 3D scaffolds fabricated from biopolymers as collagen, chitosan or fibroin. In this 3D system, cells (or a mixture of cells) are seeded in the scaffolds promoting multicellular interaction and preserving tissue cytoarchitecture. Three-dimensional fibroin (silk protein) scaffolds containing a geometrically-engineered hollow lumen mimicking the structure of the intestine (both small and large intestines) are being fabricated in our laboratory in partnership with the researcher and bioengineer Dr David L. Kaplan (Tufts University). In this system, co-cultures of intestinal epithelial cells form monolayers of polarized cells, which are nourished by surrounding myofibroblasts dispersed in the porous scaffold. These intestinal tissues represent the function of the human intestine as observed by the continuous production of a mucus layer and variable oxygen tension. The aim of this proposal is to evaluate the response of host cell to the infection with Giardia lamblia in a 3D human intestinal model compared to 2D monolayers of Caco-2 (enterocytes) and Hutu-80 (duodenum epithelial cells). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TONELLI, RENATA ROSITO; SOUZA, JULIANA BIZARRI; TSANTARLIS, KATHERINE; MONTOIA, ELISANDRA RENATA; FERRAZ, IASMIN. Giardia-Host Interactions In Vitro: 2015-2020 Review. CURRENT TROPICAL MEDICINE REPORTS, v. 8, n. 3, JUL 2021. (16/11096-7, 18/04412-5, 19/02918-1)

SILVA, MARCELO S. DA; VITARELLI, MARCELA O.; VIALA, VINCENT LOUIS; TSANTARLIS, KATHERINE; PIRES, DAVID DA SILVA; FRANCO, THIAGO A.; DE AZEVEDO, INACIO L. M. J.; ELIAS, MARIA CAROLINA; TONELLI, RENATA R.. Clues on the dynamics of DNA replication in Giardia lamblia. Journal of Cell Science, v. 136, n. 10, p. 13-pg., 2023-05-01. (17/07693-2, 20/10277-3, 18/14432-3, 13/07467-1, 14/24170-5, 19/02918-1, 20/00694-6, 16/50050-2, 19/10753-2)