Cells freshly isolated from a human thymus and human pancreatic organoids growing in culture.

Paola Bonfanti : Areas of interest

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Our research focuses on the biology of epithelial stem cells and its future clinical translation, especially in the context of tissue engineering for organ reconstruction. Epithelia line the outer and inner surfaces of our body and play crucial role in tissue homeostasis and repair. Epithelia have a complex biology, understood only in part, and despite some common features, they diversify to fulfil their specific role and function.

We aim to understand the underlying molecular and cellular mechanisms that regulate epithelia self-renewal and differentiation, with the final goal to produce long lasting, tissue engineered, medicinal products.

We primarily focus on the thymus, whose epithelial cells contribute to the microenvironment that instructs lymphoid precursors to establish proper immunity against pathogens and also to induce self-tolerance that prevents autoimmunity. We aim to dissect the components of thymus microenvironment and study their role in regulating tolerance and immune cell maturation.

Our lab is studying human epithelial oesophageal stem/progenitor cells to reconstruct a functional and growing epithelium necessary to guarantee long term repair of the epithelial barrier of the gastro-intestinal tract. We use in vitro culture systems and tissue engineering approaches to provide a functional, long-lasting epithelium for the therapy of neonatal oesophageal atresia, and other congenital and acquired disorders.

We are building also in vitro model systems to dissect fate and potency of human pancreatic progenitors. We aim at identifying intrinsic factors and environmental cues that dictate fate choices of these progenitors during pancreas development to define conditions that will allow differentiation of stem cells to insulin-producing beta-cells for possible cell therapy of diabetes.

Finally, we are exploring the use of gene-editing technology by CRISPR/Cas9 for correction of Cystic Fibrosis Trans-membrane conductance Regulator (CFTR) in airways epithelial cells in vitro.

epithelial stem cells

Figures: 1. Rhodamine-B staining of thymic epithelial colonies as they appear in culture; 2.Immunofluorescence of cultivated thymic epithelial cells (Pan-cytokeratin, green; Ki67, red; nuclei, blue); 3. Immunofluorescence of pancreatic progenitors grown in a 3D matrix (E-Cadherin, green; Sox9, red); 4.Immunohistochemistry of a developing oesophagus (P63, green; Ki67, red; nuclei, blue); 5.Immunocytochemistry of oesophageal epithelial cells as they appear in culture (Cytokeratin 13, green; Cytokeratin 14, red; nuclei, blue); 6. Normal Human Bronchial Epithelial Cells on ALI culture (Zo-1, red; ac-tubulin, green; nuclei, blue).