ArticleCirculation research2009
Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 248 citations in OpenAlex.
- Autologous peripheral blood-derived stem cells transplantation for treatment of no-option angiitis-induced critical limb ischemia: 10-year management experience.Stem cell research & therapy · 2020Trial
- The Broken Cradle: Bone Marrow Stem Cell Niche Remodelling in Diabetes.Stem cell reviews and reports · 2026Review
- Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications.Angiogenesis · 2025Review
- Isolation of endothelial progenitor cells from human adipose tissue.International journal of obesity (2005) · 2025Article
- Recent advances in the role of neuroregulation in skin wound healing.Burns & trauma · 2025Review
- Unveiling the impact of CD133 on cell cycle regulation in radio- and chemo-resistance of cancer stem cells.Frontiers in public health · 2025Review
- X-Paste improves wound healing in diabetesWorld journal of diabetes · 2024Article
- Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.Acta pharmacologica Sinica · 2024Article
- Nano hydrogel-based oxygen-releasing stem cell transplantation system for treating diabetic foot.Journal of nanobiotechnology · 2023Article
- Skin wound healing improvement in diabetic mice through FTIR microspectroscopy after implanting pluripotent stem cells.APL bioengineering · 2023Article
- Neutrophil Extracellular Traps Delay Diabetic Wound Healing by Inducing Endothelial-to-Mesenchymal Transition via the Hippo pathway.International journal of biological sciences · 2023Article
- Single-cell profiling reveals transcriptomic signatures of vascular endothelial cells in non-healing diabetic foot ulcers.Frontiers in endocrinology · 2023Article
- Circulating endothelial precursor cells are associated with a healed diabetic foot ulcer evaluated in a prospective cohort study.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2023Article
- Hematopoietic Stem Cells in Wound Healing Response.Advances in wound care · 2022Article
- Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing.Cells · 2022Review
- Glycaemic Control Achieves Sustained Increases of Circulating Endothelial Progenitor Cells in Patients Hospitalized for Decompensated Diabetes: An Observational Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022Article
- Local application reduces number of needed EPC for beneficial effects on wound healing compared to systemic treatment in mice.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022Article
- Article
- GPCR Partners as Cancer Driver Genes: Association with PH-Signal Proteins in a Distinctive Signaling Network.International journal of molecular sciences · 2021Review
- The complex role of Wnt ligands in type 2 diabetes mellitus and related complications.Journal of cellular and molecular medicine · 2021Review
60 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
We evaluated the healing potential of human fetal aorta-derived CD133(+) progenitor cells and their conditioned medium (CD133(+) CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2x10(4) CD133(+) or CD133(-) cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133(+) cells expressed high levels of wingless (Wnt) genes, which were downregulated following differentiation into CD133(-) cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133(+) cells accelerated wound closure as compared with CD133(-) or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133(+) cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133(+) CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by co-administering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133(+) CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of Wnt expression. The promigratory and proangiogenic effect of CD133(+) CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. CD133(+) cells stimulate wound healing by paracrine mechanisms that activate Wnt signaling pathway in recipients. These preclinical findings open new perspectives for the cure of diabetic ulcers.
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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 OpenQuestion graph.