ArticleJournal of translational medicine2014
Laminin 411 acts as a potent inducer of umbilical cord mesenchymal stem cell differentiation into insulin-producing cells.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Translating the blueprint of cell fate: eIF5A-mediated translation regulates cellular identity in the pancreas.Molecular metabolism · 2026Article
- Geltrex-based protocol for the differentiation of rat adipose tissue-derived mesenchymal stem cells into insulin-producing cells: in vitro and in vivo considerations.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of diabetes mellitus.Scientific reports · 2024Article
- Human umbilical cord mesenchymal stem cells in diabetes mellitus and its complications: applications and research advances.International journal of medical sciences · 2023Review
- Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip.Nature biomedical engineering · 2021Article
- Efficiency of Stem Cell (SC) Differentiation into Insulin-Producing Cells for Treating Diabetes: a Systematic Review.Stem cells international · 2021Review
- Article
- 3D-Models of Insulin-Producing β-Cells: from Primary Islet Cells to Stem Cell-Derived Islets.Stem cell reviews and reports · 2018Review
- Laminins in an in vitro anterior lens capsule model established using HLE B-3 cells.Molecular medicine reports · 2018Article
- A Novel Fragment Derived from Laminin-411 Facilitates Proliferation and Differentiation of Odontoblast-Like Cells.BioMed research international · 2018Article
- Differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells into endometrial cells.Stem cell research & therapy · 2017Article
- Infusion of umbilical cord mesenchymal stem cells alleviates symptoms of ankylosing spondylitis.Experimental and therapeutic medicine · 2017Article
- Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century.Stem cells international · 2015Review
- A fractal nature for polymerized laminin.PloS one · 2014Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetes mellitus (DM) is an incurable metabolic disease constituting a major threat to human health. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) hold great promise in the treatment of DM. The development of an efficient IPC induction system is a crucial step for the clinical application of IPCs for DM. Laminin 411 is a key component of the basement membrane and is involved in the regulation of cell differentiation; however, little is known about a role of laminin 411 in the regulation of IPC differentiation from human MSCs.
methodsMSCs were isolated from human umbilical cord (UC-MSCs) and expanded in an in vitro culture system. UC-MSCs were then cultured in the IPC induction and differentiation medium in the presence of laminin 411. Flow cytometry, Quantitative realtime PCR, immunofluorescence staining, ELISA, Western blotting and other techniques were applied to determine IPC generation, insulin expression and related mechanisms. To evaluate potential therapeutic efficacy of IPCs induced from UC-MSCs, a type-1 diabetes (T1DM) rat model was generated using streptozotocin. Blood glucose, insulin levels, and survival of rats were monitored periodically following intravenous injection of the tested cells.
resultsLaminin 411 markedly induced the expression of the genes Foxa2 and Sox17, markers for pancreatic precursor cells, efficiently induced IPC differentiation from MSCs, and up-regulated insulin expression at both mRNA and protein levels. Furthermore, the expression of the genes known to govern insulin expression including Pdx1 and Ngn3 was markedly induced by laminin 411, which suggests that Pdx1 and Ngn3 signaling pathways are involved in laminin 411 induced-insulin expression machinery. More importantly, administration of laminin 411-induced IPCs rapidly and significantly down-regulated fasting blood glucose levels, significantly reduced the HbA1c concentration and markedly improved the symptoms and survival of T1DM rats.
conclusionsOur results demonstrate that laminin 411 acts as a potent differentiation inducer of IPCs from UC-MSCs via the Pdx1 and Ngn3 signaling pathways. Moreover, transfusion of laminin 411 induced-IPCs more efficiently improves symptoms and survival of T1DM rats. These novel finding highlights a potential clinical application of laminin 411 induced-IPCs in the treatment of T1DM, which calls for further studies.
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