TEAM NET FENG

Priority 2 of the Programme: European Funds for a Modern Economy 2021–2027 (FENG)

Grant Agreement No. FENG.02.03-IP.05-0113/24

Project value (total project cost): PLN 12,344,749.02

Amount of European Funds contribution: PLN 12,344,749.02

Development of an innovative, high-throughput platform for functional screening of human pancreatic endocrine cells

About Project

Diabetes mellitus, a metabolic disorder with increasing global prevalence, arises from an imbalance in glucose metabolism. This imbalance is largely attributed to defective pancreatic beta cells, the primary producers of the hormone insulin, residing within the islets of Langerhans. Dysfunction of these beta cells leads to hyperglycemia, a condition characterized by abnormally high blood glucose concentrations. 

To expand therapeutic options for individuals with diabetes efficiently, a source of human pancreatic beta cells is crucial. Currently, the most promising avenue involves the in vitro differentiation of pluripotent stem cells into insulin-producing and secreting beta cells. Recent research from multiple laboratories worldwide, including our own, has demonstrated the potential to generate human beta cells that, in many aspects, resemble their native counterparts. 

In this study, we propose to explore the characteristics of these newly generated beta cells to improve both their quality and quantity. Furthermore, recognizing the intensive crosstalk between beta cells and other cell types within the pancreas, specifically endothelial cells, we also propose investigating the molecular nature of this communication using genomic screening, microfluidics, and in vivo diabetes models. Understanding these interactions is vital for further enhancing the accuracy and function of in vitro differentiated human beta cells. Such pancreatic organoids will offer a unique opportunity for precision in drug discovery. 

Three-dimensional (3D) cultures containing pancreatic beta cells that express insulin (green) and NKX6-1 (red). Nuclei are labeled with DAPI (blue).
Human pluripotent stem cell (hPSC)-derived pancreatic beta cells expressing insulin (green) and E-cadherin (red), with nuclei stained using DAPI (blue). The image was captured using a super-resolution Elyra microscope.
(upper panel) The Lightsheet microscopy image of the developing pancreas and nearby organs in a mouse embryo at 16.5 days. Spleen, along with parts of the stomach and intestine are also visible. The green areas highlight insulin-producing beta cells in the pancreas, white shows blood vessels, and red marks mesenchyme.
(lower panel) 3D model of the developing pancreas and its microenvironment in a 12.5-day-old mouse embryo. Green spots represent beta cells, while the white and red areas indicate blood vessels and mesenchyme.

Project Team

  1. Uniwersytet im. Adama Mickiewicza w Poznaniu – prof. UAM dr hab. Małgorzata Borowiak – Instytut Biologii Molekularnej i Biotechnologii – Zakład Ekspresji Genów – https://ibmib.web.amu.edu.pl/groups/stem-cell-laboratory/
  2. Uniwersytet Warszawski – dr inż. Tomasz Kamiński – Instytut Biochemii -Zakład Biologii Molekularnej –https://www.biol.uw.edu.pl/jednostki-naukowo-dydaktyczne/instytut-biochemii/zaklad-biologii-molekularnej/
  3. Uniwersytet Jagielloński -Prof. dr hab. Józef Dulak -Wydział Biochemii, Biofizyki i Biotechnologii UJ -Zakład Biotechnologii Medycznej –https://zbm.wbbib.uj.edu.pl/kontakt1

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