UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Investigating human pancreas development in a dish

Campinoti, Sara; (2021) Investigating human pancreas development in a dish. Doctoral thesis (Ph.D), UCL (University College London).

[thumbnail of CampinotiThesis-Revised March 2021.pdf] Text
CampinotiThesis-Revised March 2021.pdf - Accepted version
Access restricted to UCL open access staff until 1 April 2023.

Download (14MB)

Abstract

Efforts are underway to develop cell therapies for diabetes using endocrine cells derived in vitro from human pluripotent stem cells. However, protocols are hampered by a scarcity of knowledge on human pancreatic development and on how to model endocrine differentiation of pancreatic progenitors in vitro. In this thesis, gene expression, Fluorescence Activated Cell Sorting (FACS) and immunohistochemical analyses were used, along with other techniques, to provide systematic characterisation of pancreatic cell populations during ontogenesis. Human fetal pancreatic progenitor cells (hPPCs) were successfully isolated from pancreatic tissue of different embryonic and fetal stages. hPPCs were extensively cultivated in 3D MatrigelTM cultures in Expansion Medium (EM), and in Organogenesis Medium (OM), to assess their multipotent nature. Freshly isolated or expanded hPPCs were triggered to differentiate into endocrine cells; notably a significant increase of endocrine markers was observed at gene and protein levels, even after extensive expansion. 3D organoid cultures rely mostly on MatrigelTM, a hydrogel derived from mouse sarcoma which is not suitable for clinical application. To overcome this, hPPC cultures were established utilizing fully synthetic, functionalised hydrogels with defined physical properties and also by producing hydrogels from native extracellular matrix (ECM). Cell growth and differentiation potency were modulated by ECM properties, opening the possibility of directing cell fate by integrating soluble factors, matrix components and cell-cell interaction mechanisms. In conclusion, this thesis provides a comprehensive characterisation of human embryonic and fetal pancreas, and addresses human pancreatic progenitor potency in clinically relevant culture conditions.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating human pancreas development in a dish
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10122855
Downloads since deposit
3Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item