ArticleStem cell research & therapy2022
Melatonin treatment improves human umbilical cord mesenchymal stem cell therapy in a mouse model of type II diabetes mellitus via the PI3K/AKT signaling pathway.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 72 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Human Umbilical Cord Mesenchymal Stem Cells in Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) Therapy: Mechanisms, Clinical Efficacy, and Future Perspectives.Stem cell reviews and reports · 2026Review
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- Integrated transcriptomic and metabolomic analyses reveal the regulatory mechanism of subcutaneous fat deposition in Baicheng Oil chickens.Poultry science · 2026Article
- Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation.Journal of pharmaceutical analysis · 2026Review
- Clinical Efficacy of SPARC-Modified Mesenchymal Stem Cells for the Treatment of Dog Skin Wounds.Veterinary sciences · 2026Article
- Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review).Molecular medicine reports · 2026Review
- The protection of mesenchymal stem cells in metabolic reprogramming and endothelial-mesenchymal transition in diabetic aortas.Stem cells translational medicine · 2026Article
- Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes.Drug design, development and therapy · 2026Review
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- Porcine cells restrict human cell proliferation via cellular competition in a human-porcine mesenchymal stem cells co-culture model.Frontiers in cell and developmental biology · 2026Article
- Combination of 20(R)-Rg3 and HUCMSCs Alleviates Type 2 Diabetes Mellitus in C57BL/6 Mice by Activating the PI3K/Akt Signaling Pathway.International journal of molecular sciences · 2025Article
- Mechanisms of gypenosides in type 2 diabetes mellitus via regulation of m6A methylase METTL3/14 and demethylase FTO.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Human umbilical cord mesenchymal stem cells ameliorates cisplatin-induced blood-testis barrier dysfunction in mice by mitigating ferroptosis.Stem cell research & therapy · 2025Article
- Melatonin and angiogenesis potential in stem cells.Stem cell research & therapy · 2025Review
- 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
- Melatonin Interplay in Physiology and Disease-The Fountain of Eternal Youth Revisited.Biomolecules · 2025Review
- Functional analysis ofThe Journal of general virology · 2025Article
- Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.American journal of physiology. Heart and circulatory physiology · 2025Article
- Article
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21 authors at 4 institutions in 1 country.
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Abstract
backgroundMesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSC therapy. This study investigated whether the combination of melatonin and human umbilical cord mesenchymal stem cells (hUC-MSCs) was superior to hUC-MSCs alone in ameliorating high-fat diet and streptozocin (STZ)-induced type II diabetes mellitus (T2DM) in a mouse model.
methodsMice were divided into four groups: normal control (NC) group; T2DM group; hUC-MSCs treatment alone (UCMSC) group and pretreatment of hUC-MSCs with melatonin (UCMSC/Mel) group.
resultsRNA sequence analysis showed that certain pathways, including the signaling pathway involved in the regulation of cell proliferation signaling pathway, were regulated by melatonin. The blood glucose levels of the mice in the UCMSC and UCMSC/Mel treatment groups were significantly reduced compared with the T2DM group without treatment (P < 0.05). Furthermore, hUC-MSCs enhance the key factor in the activation of the PI3K/Akt pathway in T2DM mouse hepatocytes.
conclusionThe pretreatment of hUC-MSCs with melatonin partly boosted cell efficiency and thereby alleviated impaired glycemic control and insulin resistance. This study provides a practical strategy to improve the application of hUC-MSCs in diabetes mellitus and cytotherapy. Overview of the PI3K/AKT signaling pathway. (A) Underlying mechanism of UCMSC/Mel inhibition of hyperglycemia and insulin resistance T2DM mice via regulation of PI3K/AKT pathway. hUC-MSCs stimulates glucose uptake and improves insulin action thus should inhibition the clinical signs of T2DM, through activation of the p-PI3K/Akt signaling pathway and then regulates glucose transport through activating AS160. UCMSC/Mel increases p53-dependent expression of BCL2, and inhibit BAX and Capase3 protein activation. Leading to the decrease in apoptosis. (B) Melatonin modulated PI3K/AKT signaling pathway. Melatonin activated PI3K/AKT response pathway through binding to MT1and MT2 receptor. Leading to the increase in hUC-MSCs proliferation, migration and differentiation. → (Direct stimulatory modification); ┴ ( Direct Inhibitory modification); → ┤ (Multistep inhibitory modification); ↑ (Up regulate); ↓ (Down regulate); PI3K (Phosphoinositide 3-Kinase); AKT ( protein kinase B); PDK1 (Phosphoinositide-dependent protein kinase 1); IR, insulin receptor; GLUT4 ( glucose transporter type 4); ROS (reactive oxygen species); BCL-2 (B-cell lymphoma-2); PDK1 (phosphoinositide-dependent kinase 1) BAX (B-cell lymphoma-2-associated X protein); PCNA (Proliferating cell nuclear antigen); Cell cycle-associated proteins (KI67, cyclin A, cyclin E).
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