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The Influence of GLP-1 Agonists on Human Mesenchymal Stem Cells: A Systematic Review
Luisa Weber1, Maryam Hashemnia Sharbabaki2, Benedikt Fuchs2
1Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, Munich, Germany. luisa.weber@med.uni-muenchen.de.
Background:
Glucagon-like peptide-1 receptor agonists, originally developed for managing type 2 diabetes, have gained attention for their weight-reducing and broader biological effects. Among these, their influence on human mesenchymal stem cells remains underexplored, despite the critical role of mesenchymal stem cells in tissue regeneration and secretion of bioactive factors.
Methods:
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify and evaluate in vitro studies investigating the effects of glucagon-like peptide-1 receptor agonists and their analogues on human mesenchymal stem cell functions, including proliferation, differentiation, signaling, apoptosis, and tissue-specific applications. Risk of bias was assessed using an adapted Quality Assessment Tool for In Vitro Studies (QUIN) tool.
Results:
Thirty-eight eligible studies were identified. Glucagon-like-peptide-1 receptor agonist, like native glucagon-like peptide-1, Exendin-4, and Liraglutide, exert context-, dose-, and timing-dependent effects on human mesenchymal stem cells. They modulate proliferation and overall promote osteogenesis while inhibiting adipogenesis. Key pathways, including Wnt/β-catenin, bone morphogenetic protein 2/Smad, phosphoinositide 3-kinase/Akt and protein kinase A, play a role in this. Furthermore, these agents modulate inflammation, reduce apoptosis, and improve stem cell functions even under diabetic or inflammatory conditions. Exendin-4 facilitated tenogenic and insulin-producing cell differentiation, particularly in engineered scaffolds or genetically engineered human mesenchymal stem cells.
Conclusion:
Glucagon-like peptide-1 receptor agonists modulate key pathways in human mesenchymal stem cells to influence survival, differentiation, and metabolic function, suggesting promising therapeutic potential beyond glycemic control. However, heterogeneous experimental designs and limited translational data necessitate further standardized and in vivo research to define clinical applications.
Insights
Glucagon-like peptide-1 receptor agonists impact human mesenchymal stem cells, influencing their survival, differentiation, and metabolic functions. These findings suggest potential therapeutic uses beyond diabetes management, warranting further research.
Area of Science:
- Stem Cell Biology
- Pharmacology
- Regenerative Medicine
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established type 2 diabetes treatments with recognized weight-reducing effects.
- Their broader biological impacts, particularly on human mesenchymal stem cells (hMSCs), are less understood.
- hMSCs are crucial for tissue regeneration and secrete vital bioactive factors.
Purpose of the Study:
- To systematically review in vitro studies on GLP-1 RAs' effects on hMSC functions.
- To evaluate impacts on proliferation, differentiation, signaling, apoptosis, and specific tissue applications.
- To assess the quality of included in vitro studies.
Main Methods:
- Systematic literature search adhering to PRISMA guidelines.
- Inclusion of in vitro studies examining GLP-1 RAs and hMSC interactions.
- Risk of bias assessment using the Quality Assessment Tool for In Vitro Studies (QUIN).
Main Results:
- Thirty-eight studies revealed context-, dose-, and timing-dependent effects of GLP-1 RAs on hMSCs.
- GLP-1 RAs modulate proliferation, promote osteogenesis, and inhibit adipogenesis.
- Key pathways (Wnt/β-catenin, BMP2/Smad, PI3K/Akt, PKA) are involved; inflammation and apoptosis are modulated, improving hMSC function in adverse conditions.
Conclusions:
- GLP-1 RAs modulate hMSC survival, differentiation, and metabolism via key signaling pathways.
- These agents show therapeutic promise beyond glycemic control.
- Further standardized in vivo research is needed due to experimental heterogeneity and limited translational data.

