Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats

Kong, Poren; Xie, Xiaoyun; Fang, Li; Liu, Yang; Lu, Yingli

doi:10.1016/j.bbrc.2013.07.088

Cited by 120 publications

(99 citation statements)

References 33 publications

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“…Our previous studies demonstrated that MSCs derived from human umbilical cords could efficiently repair ischemia and reperfusion-induced acute kidney injury and carbon tetrachlorideinjured hepatic injury [7,8,36]. MSCs have been shown to perform their therapeutic roles by promoting angiogenesis [37][38][39]. It is generally accepted that transplanted MSCs promote angiogenesis mainly through paracrine mechanisms [40].…”

Section: Discussionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Zhang

et al. 2015

Stem Cells Translational Medicine

364

298

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Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted b-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and b-catenin and the decreased expression of E-cadherin. The activation of Wnt/b-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by b-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated b-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces b-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing. STEM CELLS TRANSLATIONAL MEDICINE 2015; 4:513-522 SIGNIFICANCEHuman umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, it is reported that hucMSC-Ex-mediated Wnt4 induces b-catenin activation in endothelial cells and exerts proangiogenic effects, which could be one of the important mechanisms responsible for cutaneous wound healing.

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Section: Discussionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Zhang

et al. 2015

Stem Cells Translational Medicine

364

298

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“…Wounds treated with MSCs in these reports have shown a qualitative improvement regarding histological characteristics, such as superior rete ridge architecture, multi-layered structure, improved dermalepidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [120][121][122][123].…”

Section: Msc-related Therapy For Diabetic Woundsmentioning

confidence: 99%

“…Successful wound healing is particularly related to the secretion of trophic factors, such as VEGF, IGF-1, bFGF, PDGF-BB, Ang-1, SDF-1, EGF, KGF and MMP9, or cytokines, such as TGF-β, IL6 and IL8. These could contribute towards wound repair and skin regeneration by suppressing inflammation, angiogenesis and stimulating skin stem cell proliferation and differentiation into new keratinocytes [123,131,[135][136][137][138].…”

Section: Msc-related Therapy For Diabetic Woundsmentioning

confidence: 99%

“…MSCs have been used to date in treating different skin disorders [20,118,119]; several groups have reported successful wound healing in pre-clinical models of diabetic wounds after the administration of autologous or allogeneic MSCs from different sources [120][121][122][123]. Wounds treated with MSCs in these reports have shown a qualitative improvement regarding histological characteristics, such as superior rete ridge architecture, multi-layered structure, improved dermalepidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [120][121][122][123].…”

Section: Msc-related Therapy For Diabetic Woundsmentioning

confidence: 99%

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Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

Ezquer

Arango-Rodríguez²,

Giraud-Billoud³

et al. 2014

J Stem Cell Res Ther

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“…Among all types of stem cells, mesenchymal stem cells remain to be one of the most attractive and main sources for stem cell-based therapy due to their minimal tumorogenicity [3,4] and immunogenicity [5], combined with their ease of accessibility [6]. Mesenchymal stem cells (MSCs) can be derived from various tissues and can similarly differentiate into numerous cell types.…”

Section: Introductionmentioning

confidence: 99%

Delivery of Placenta-Derived Mesenchymal Stem Cells Ameliorates Ischemia Induced Limb Injury by Immunomodulation

Zhang

Adesanya

Zhang

et al. 2014

Cell Physiol Biochem

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Background: Peripheral artery disease (PAD) is a major health burden in the world. Stem cell-based therapy has emerged as an attractive treatment option in regenerative medicine. In this study, we sought to test the hypothesis that stem cell-based therapy can ameliorate ischemia induced limb injury. Methods: We isolated mesenchymal stem cells derived from human placentas (PMSCs) and intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs reduced acute muscle fibers apoptosis induced by ischemia. Results: PMSC treatment significantly enhanced regeneration of the injured hind limb by reducing fibrosis and enhancing running capacity when the animals were subjected to treadmill training. Mechanistically, injected PMSCs can modulate acute inflammatory responses by reducing neutrophil and macrophage infiltration following limb ischemia. ELISA assays further confirmed that PMSC treatment can also reduce pro-inflammatory cytokines, TNF-α and IL-6, and enhance anti-inflammatory cytokine, IL-10 at the injury sites. Conclusion: Taken together, our results demonstrated that PMSCs can be a potential effective therapy for treatment of PAD via immunomodulation.

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Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats

Cited by 120 publications

References 33 publications

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

Delivery of Placenta-Derived Mesenchymal Stem Cells Ameliorates Ischemia Induced Limb Injury by Immunomodulation

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