ArticleCytotherapy2018
Functional organic cation transporters mediate osteogenic response to metformin in human umbilical cord mesenchymal stromal cells.
Article in Cytotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Combination of Periodontal Ligament Stem Cells and Metformin via Organic Cation Transporters for Periodontal Regeneration in Rats.Biomolecules · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Improvement of osteogenic differentiation potential of placenta-derived mesenchymal stem cells by metformin via AMPK pathway activation.Stem cell research & therapy · 2024Article
- Bone Loss in Diabetes Mellitus: Diaporosis.International journal of molecular sciences · 2024Review
- Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging.Frontiers in pharmacology · 2024Review
- Research Progress on the Osteogenesis-Related Regulatory Mechanisms of Human Umbilical Cord Mesenchymal Stem Cells.Stem cell reviews and reports · 2023Review
- mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.International journal of molecular sciences · 2023Review
- Impact of Metformin on Periodontal and Peri-Implant Soft and Hard Tissue.International journal of environmental research and public health · 2023Review
- Effects of Metformin Delivery via Biomaterials on Bone and Dental Tissue Engineering.International journal of molecular sciences · 2022Review
- Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways.Stem cell research & therapy · 2022Review
- Article
- Effect of metformin on stem cells: Molecular mechanism and clinical prospect.World journal of stem cells · 2020Review
- Local Application of Semaphorin 3A Combined with Adipose-Derived Stem Cell Sheet and Anorganic Bovine Bone Granules Enhances Bone Regeneration in Type 2 Diabetes Mellitus Rats.Stem cells international · 2019Article
- Metformin from mother to unborn child - Are there unwarranted effects?EBioMedicine · 2018Review
- Novel Calcium Phosphate Cement with Metformin-Loaded Chitosan for Odontogenic Differentiation of Human Dental Pulp Cells.Stem cells international · 2018Article
- Osteogenic Induction of Wharton's Jelly-Derived Mesenchymal Stem Cell for Bone Regeneration: A Systematic Review.Stem cells international · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundCompelling evidence indicates that metformin, a low-cost and safe orally administered biguanide prescribed to millions of type 2 diabetics worldwide, induces the osteoblastic differentiation of mesenchymal stromal cells (MSCs) through the 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway. As a highly hydrophilic cationic compound, metformin uptake is facilitated by cell membrane organic cation transporters (OCTs) of the solute carrier 22A gene family. We hypothesized that to effectively enhance osteogenic differentiation, and ultimately bone regeneration, metformin must gain access into functional OCT-expressing MSCs.
methodsData was obtained through immunoblotting, cellular uptake, mineralization and gene expression assays.
resultsWe demonstrate for the first time that functional OCTs are expressed in human-derived MSCs from umbilical cord Wharton's jelly, an inexhaustible source of nonembryonic MSCs with proven osteogenic potential. A clinically relevant concentration of metformin led to AMPK activation, enhanced mineralized nodule formation and increased expression of the osteogenic transcription factor Runt-related transcription factor 2 (RUNX2). Indeed, targeting OCT function through pharmacological and genetic approaches markedly blunted these responses.
conclusionsOur findings indicate that functional OCT expression in UC-MSCs is a biological prerequisite that facilitates the intracellular uptake of metformin to induce an osteogenic effect. Future pre-clinical studies are warranted to investigate whether the expression of functional OCTs may serve as a potential biomarker to predict osteogenic responses to metformin.
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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 Socratic graph.