Neonatal pancreatic pericytes support β-cell proliferation
Alona Epshtein1, Eleonor Rachi1, Lina Sakhneny1
1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Insights
Neonatal pancreatic pericytes are essential for beta-cell proliferation. These cells support the growth of beta-cells, crucial for maintaining insulin production and potentially treating diabetes.
Area of Science:
- Endocrinology
- Cell Biology
- Developmental Biology
Background:
- Beta-cell mass is critical for insulin production and is maintained by cell proliferation, primarily during the neonatal period.
- The islet microenvironment, including vascular cells, plays a role in regulating beta-cell proliferation.
Purpose of the Study:
- To investigate the role of pancreatic pericytes, a component of islet vasculature, in supporting neonatal beta-cell proliferation.
- To test the hypothesis that pericytes are key regulators of beta-cell growth in neonates.
Main Methods:
- In vivo studies utilized a diphtheria toxin-based transgenic mouse model to specifically deplete neonatal pancreatic pericytes.
- In vitro experiments involved culturing isolated neonatal pancreatic pericytes and using beta-cell lines and primary mouse beta-cells.
Main Results:
- Depletion of neonatal pancreatic pericytes in vivo led to impaired neonatal beta-cell proliferation.
- Conditioned medium from pericytes stimulated proliferation in cultured beta-cells, indicating pericytes are sufficient for this effect.
Conclusions:
- Neonatal pancreatic pericytes are identified as crucial regulators of neonatal beta-cell proliferation.
- These findings enhance understanding of physiological beta-cell replication and may inform strategies for cell expansion in diabetes therapy.
Objective:
The maintenance and expansion of β-cell mass rely on their proliferation, which reaches its peak in the neonatal stage. β-cell proliferation was found to rely on cells of the islet microenvironment. We hypothesized that pericytes, which are components of the islet vasculature, support neonatal β-cell proliferation.
Methods:
To test our hypothesis, we combined in vivo and in vitro approaches. Briefly, we used a Diphtheria toxin-based transgenic mouse system to specifically deplete neonatal pancreatic pericytes in vivo. We further cultured neonatal pericytes isolated from the neonatal pancreas and combined the use of a β-cell line and primary cultured mouse β-cells.
Results:
Our findings indicate that neonatal pancreatic pericytes are required and sufficient for β-cell proliferation. We observed impaired proliferation of neonatal β-cells upon in vivo depletion of pancreatic pericytes. Furthermore, exposure to pericyte-conditioned medium stimulated proliferation in cultured β-cells.
Conclusions:
This study introduces pancreatic pericytes as regulators of neonatal β-cell proliferation. In addition to advancing current understanding of the physiological β-cell replication process, these findings could facilitate the development of protocols aimed at expending these cells as a potential cure for diabetes.
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