ArticleStem cell research & therapy2021
Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Mechanical stretch loading of BMSCs-PLCL composite scaffolds accelerate diabetic wound healing by protecting endothelial cells and promoting angiogenesis.Stem cell research & therapy · 2026Article
- Extracellular vesicles-delivered circDB promotes ischemic muscle repair through the miR-34a/USP7/Notch1 signaling pathway.Regenerative therapy · 2025Article
- Naringenin boosts Parkin-mediated mitophagy via estrogen receptor alpha to maintain mitochondrial quality control and heal diabetic foot ulcer.Journal of pharmaceutical analysis · 2025Article
- The contribution of probiotics to combined cellular therapy in skin wound healing in diabetic rats.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2025Article
- Current perspectives on regenerative potential of mesenchymal stem cells in alleviating cardiac injuries: Molecular pathways and therapeutic enhancement.World journal of stem cells · 2025Review
- SDF-1α loaded lipid liquid crystalline hydrogel accelerates diabetic wound healing in in vitro and in vivo models.Scientific reports · 2025Article
- Research progress on the mechanism underlying the application of mesenchymal stem cells in the treatment of male infertility.Frontiers in endocrinology · 2025Review
- Advances in Stem Cell Therapy for Diabetic Foot Ulcers.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Recombinant human fibronectin segment (rhFNRegenerative biomaterials · 2025Article
- The Potential of Mesenchymal Stem/Stromal Cells in Diabetic Wounds and Future Directions for Research and Therapy-Is It Time for Use in Everyday Practice?International journal of molecular sciences · 2024Review
- Enhancement of cardiac angiogenesis in a myocardial infarction rat model using selenium alone and in combination with PTXF: the role of Akt/HIF-1α signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Murine bone-derived mesenchymal stem cells undergo molecular changes after a single passage in culture.Scientific reports · 2024Article
- Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions.Journal of diabetes · 2024Review
- Emerging delivery approaches for targeted pulmonary fibrosis treatment.Advanced drug delivery reviews · 2024Review
- Advances in stem cell therapy for diabetic foot.Frontiers in genetics · 2024Review
- Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.International wound journal · 2023Review
- External Application of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Hyaluronic Acid Gel Repairs Foot Wounds of Types I and II Diabetic Rats Through Paracrine Action Mode.Stem cells translational medicine · 2023Article
- Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles.Bioactive materials · 2023Article
- Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review.Medicina (Kaunas, Lithuania) · 2023Review
- Male or female sex: considerations and translational aspects in diabetic foot ulcer research using rodent models.Molecular and cellular biochemistry · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms.
methodA diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis.
resultBoth topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway.
conclusionsThe results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.
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