ArticleStem cells translational medicine2023
Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.
Article in Stem cells translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Co-transplantation of pancreatic islets with adipose-derived mesenchymal stem cells in vascularized kidney ECM scaffolds to restore type 1 diabetes mellitus.Bioactive materials · 2026Article
- The key regulation of LncRNA MALAT during reprogramming of primary mouse hepatocytes into insulin producing cells.Scientific reports · 2025Article
- In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.Diabetes & metabolism journal · 2025Article
- Low-intensity ultrasound stimulation promotes differentiation of bone marrow mononuclear cells to nucleus pulposus cells for matrix synthesis.American journal of translational research · 2025Article
- Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus.Stem cell research & therapy · 2024Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs. BMNCs cultured under the defined conditions synergistically expressed multiple genes, including those for PDX1, NKX6.1, MAFA, NEUROG3, GLUT2, and insulin, related to pancreatic beta cell development and function. They produced insulin/C-peptide and PDX1, as assessed using immunofluorescence and flow cytometry. The induced cells secreted insulin in a glucose-responsive manner, similar to normal pancreatic beta cells. Grafting BMNC-derived IPCs under kidney capsules of mice with streptozotocin (STZ)-induced diabetes alleviated hyperglycemia by lowering blood glucose levels, enhancing glucose tolerance, and improving glucose-stimulated insulin secretion. Insulin- and PDX1-expressing cells were observed in the IPC-bearing graft sections of nephrectomized mice. Therefore, this study provides a simple protocol for BMNC differentiation, which can be a novel approach for cell-based therapy in diabetes mellitus.
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Registered trials
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