ArticleScience advances2021
Exendin-4 gene modification and microscaffold encapsulation promote self-persistence and antidiabetic activity of MSCs.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- The Influence of GLP-1 Agonists on Human Mesenchymal Stem Cells: A Systematic Review.Stem cell reviews and reports · 2026Pooled it
- A meta-analysis on application and prospect of cell therapy in the treatment of diabetes mellitus.Stem cell research & therapy · 2025Pooled it
- Stem cell therapies for treatment of diabetes mellitus.Chinese medical journal · 2026Review
- METTL1-deficient mesenchymal stem cells protect against metabolic-associated fatty liver disease by increasing NAMPT secretion.Stem cells translational medicine · 2026Article
- The progress and challenges of mesenchymal stromal cell-based therapy for diabetes and its complications.Biological research · 2026Review
- Systemic effects of type 2 diabetes therapies: an integrated perspective on the cardio-renal- cerebral-metabolic axis.Frontiers in medicine · 2026Review
- Engineered 3D mesenchymal stem cell aggregates with multifunctional prowess for bone regeneration: Current status and future prospects.Journal of advanced research · 2026Review
- The role and mechanism of mesenchymal stem cells in immunomodulation of type 1 diabetes mellitus and its complications: recent research progress and challenges: a review.Stem cell research & therapy · 2025Review
- Multiplexing 3D Natural Scaffolds to Optimize the Repair and Regeneration of Chronic Diabetic Wounds.Gels (Basel, Switzerland) · 2025Review
- Glucagon-like peptide-1: a new potential regulator for mesenchymal stem cells in the treatment of type 2 diabetes mellitus and its complication.Stem cell research & therapy · 2025Review
- Knockout of B2M in combination with PD-L1 overexpression protects MSC-derived new islet β cells from graft rejection in the treatment of canine diabetes mellitus.Stem cell research & therapy · 2024Article
- Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management.Stem cell research & therapy · 2024Review
- Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine β-Synthase Mediated IL-6/STAT3 Inactivation.Biomolecules · 2024Article
- Enhanced bone regeneration via endochondral ossification using Exendin-4-modified mesenchymal stem cells.Bioactive materials · 2024Article
- Exendin-4-enriched exosomes from hUCMSCs alleviate diabetic nephropathy via gut microbiota and immune modulation.Frontiers in microbiology · 2024Article
- Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: a bioinformatics analysis.Frontiers in endocrinology · 2024Article
- Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy.eLife · 2023Article
- Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche.Nature communications · 2023Article
- Injectable bone marrow microniches by co-culture of HSPCs with MSCs in 3D microscaffolds promote hematopoietic reconstitution from acute lethal radiation.Bioactive materials · 2023Article
- Scar-Degrading Endothelial Cells as a Treatment for Advanced Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cell (MSC)-based therapy to combat diabetic-associated metabolic disorders is hindered by impoverished cell survival and limited therapeutic effects under high glucose stress. Here, we genetically engineered MSCs with Exendin-4 (MSC-Ex-4), a glucagon-like peptide-1 (GLP-1) analog, and demonstrated their boosted cellular functions and antidiabetic efficacy in the type 2 diabetes mellitus (T2DM) mouse model. Mechanistically, MSC-Ex-4 achieved self-augmentation and improved survival under high glucose stress via autocrine activation of the GLP-1R-mediated AMPK signaling pathway. Meanwhile, MSC-Ex-4-secreted Exendin-4 suppressed senescence and apoptosis of pancreatic β cells through endocrine effects, while MSC-Ex-4-secreted bioactive factors (e.g., IGFBP2 and APOM) paracrinely augmented insulin sensitivity and decreased lipid accumulation in hepatocytes through PI3K-Akt activation. Furthermore, we encapsulated MSC-Ex-4 in 3D gelatin microscaffolds for single-dose administration to extend the therapeutic effect for 3 months. Together, our findings provide mechanistic insights into Exendin-4-mediated MSCs self-persistence and antidiabetic activity that offer more effective MSC-based therapy for T2DM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.