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Published on: March 1, 2024
In the search of potential human islet stem cells: is tetranectin showing us the way?
M Hermann1, D Pirkebner, A Draxl
1KMT Laboratory, University Hospital of Innsbruck, Innsbruck, Austria. martin.hermann@uibk.ac.at
Abstract:
Pancreatic islet cell transplantation is a promising approach to restore the required mass of functional beta cells in diabetic patients as a means to achieve long-term normoglycemia. This therapy is, however, not yet widely used, in part because of the shortage of human islet cells. Gaining detailed knowledge of the physiological basis governing the processes of differentiation of pancreatic stem or progenitor cells and the mechanisms and molecules necessary for a successful engraftment of the transplanted cells into the liver is instrumental for the ambitious goal of engineering new pancreatic islets to cure type I diabetes. We describe the in vivo and in vitro localisation of tetranectin (TN) in human and murine islet cells. Similar to human islets, murine islets stain positive for tetranectin. The amount and localization of TN is influenced by different culture conditions. The ability of TN to bind plasminogen indicates that it may have a role in regulating pericellular proteolysis and proteolytic activation of latent forms of metalloproteinases and growth factors. Tetranectin may thereby play an important role in the survival of islets in the liver after islet transplantation. TN-positive cells can be isolated and maintained in culture after human islet isolation, thereby providing the possibility to further clarify its role and function in vivo as well as in the course of islet transplantation.
Insights
Tetranectin (TN) is found in human and mouse islet cells, potentially aiding transplanted islet survival in the liver. This discovery offers new avenues for treating type 1 diabetes through improved islet transplantation.
Area of Science:
- Endocrinology
- Cell Biology
- Regenerative Medicine
Background:
- Pancreatic islet cell transplantation aims to cure type 1 diabetes by restoring beta cell function.
- A shortage of human islet cells limits the widespread use of this therapy.
- Understanding islet cell differentiation and engraftment is crucial for engineering new islets.
Purpose of the Study:
- To investigate the localization of tetranectin (TN) in human and murine islet cells.
- To explore the potential role of TN in islet cell survival after transplantation.
- To assess the feasibility of isolating TN-positive cells for further research.
Main Methods:
- Immunohistochemical staining for tetranectin in human and murine islet cells.
- In vitro and in vivo localization studies of tetranectin.
- Analysis of TN's interaction with plasminogen and its potential role in proteolysis.
Main Results:
- Tetranectin was localized in both human and murine islet cells.
- TN localization and amount were affected by cell culture conditions.
- TN's plasminogen-binding ability suggests a role in regulating pericellular proteolysis.
Conclusions:
- Tetranectin may play a significant role in the survival of transplanted islets in the liver.
- TN-positive cells can be isolated from human islets, enabling further in vivo and transplantation-related functional studies.