Human Cord Blood-Derived Endothelial Progenitor Cells and Their Conditioned Media Exhibit Therapeutic Equivalence for Diabetic Wound Healing

Kim, Ji Yeon; Song, Sun-Hwa; Kim, Koung Li; Ko, Jeong-Jae; Im, Ji-Eun; Yie, Se Won; Ahn, Young Keun; Kim, Duk Kyung; Suh, Wonhee

doi:10.3727/096368910x516637

Cited by 102 publications

(83 citation statements)

References 27 publications

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“…Similar results have been reported for the treatment of diabetic dermal wounds. The injection of EPC-CM into wounded diabetic mice promoted wound healing and increased neovascularization to a similar extent to EPC transplantation [36]. In the present study, we demonstrated that cerebral ischemic injury was mitigated by the administration of EPC-CM in a mouse stroke model.…”

Section: Discussionsupporting

confidence: 54%

Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice

Bao¹,

Liu²,

Yang³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Prolonged fasting (PF) was shown to be of great potency to promote optimal health and reduce the risk of many chronic diseases. This study sought to determine the effect of PF on the endothelial progenitor cell (EPC)-mediated angiogenesis in the ischemic brain and cerebral ischemic injury in mice. Methods: Mice were subjected to PF or periodic PF after cerebral ischemia, and histological analysis and behavioral tests were performed. Mouse EPCs were isolated and examined, and the effects of EPC transplantation on cerebral ischemic injury were investigated in mice. Results: It was found that PF significantly increased the EPC functions and angiogenesis in the ischemic brain, and attenuated the cerebral ischemic injury in mice that was previously subjected to cerebral ischemia. Periodic PF might reduce cortical atrophy and improve long-term neurobehavioral outcomes after cerebral ischemia in mice. The eNOS and MnSOD expression and intracellular NO level were increased, and TSP-2 expression and intracellular O₂^- level were reduced in EPCs from PF-treated mice compared to control. In addition, transplanted EPCs might home into ischemic brain, and the EPCs from PF-treated mice had a stronger ability to promote angiogenesis in ischemic brain and reduce cerebral ischemic injury compared to the EPCs from control mice. The EPC-conditioned media from PF-treated mice exerted a stronger effect on cerebral ischemic injury reduction compared to that from control mice. Conclusion: Prolonged fasting promoted EPC-mediated ischemic angiogenesis and improved long-term stroke outcomes in mice. It is implied that prolonged fasting might potentially be an option to treat ischemic vascular diseases.

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Section: Discussionsupporting

confidence: 54%

Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice

Bao¹,

Liu²,

Yang³

et al. 2016

Cell Physiol Biochem

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“…However, the induction of wound closure was not statistically different compared to the control for the remaining time points [23]. There was a report demonstrating that transplantation of endothelial progenitor cells could enhance keratinocyte and fibroblast proliferation, inducing wound closure as early as day 3 posttransplantation [33]. These discrepancies between the rates of wound closure could be due to multiple factors, such as the quantity of the injected cells, the different types of cell, the use of expanded or freshly isolated cells, the engraftment procedure, and the species of mouse.…”

Section: Discussionmentioning

confidence: 99%

“…For the paracrine effect, one study showed that the conditioned medium of the hematopoietic progenitor cell line of DKmix cells could promote angiogenesis within wounds in murine models [27]. Moreover, conditioned media of human CB-derived endothelial progenitor cells have been found to promote keratinocyte, fibroblast and endothelial cell proliferations in a paracrine manner in the same action performed by the injection of endothelial progenitor cells into wounds on diabetic mice [33]. These data demonstrate that the incorporated stem cells release cytokines that act in a paracrine manner to enhance neovascularization, resulting in the remodeling of extracellular matrix and recruitment of circulating stem cells.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells

Chotinantakul¹,

Dechsukhum²,

Dejjuy³

et al. 2013

Cellular and Molecular Biology Letters

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Diabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34 + cells (CB-CD34 + cells), freshly isolated CB-CD34 + cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34 + cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34 + cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34 + cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34 + cells and the cytokine cocktail were shown to promote recruitment of CD31 + -endothelial cells in the wounds. Both the CB-CD34 + cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34 + cells or freshly isolated CB-CD34 + cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34 + cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34 + cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.

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“…2,21,26,27 However, these studies could not predict accurate therapeutic outcomes in humans, as these observations were based in immunodeficient mouse models. In an attempt to provide a more reliable prediction, we assessed the therapeutic efficacy of CB-EPCs and hESCECs after transplantation of these cells into hu-mice after surgically creating hindlimb ischemia ( Figure 4A).…”

Section: Comparison Of Therapeutic Efficacies For Improving Blood Flomentioning

confidence: 99%

Therapeutic Efficacy of Human Embryonic Stem Cell–Derived Endothelial Cells in Humanized Mouse Models Harboring a Human Immune System

Yang

Moon

Choi

et al. 2013

ATVB

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Objective-Allogeneic transplantation of human embryonic stem cell (hESC) derivatives has the potential to elicit the patient's immune response and lead to graft rejection. Although hESCs and their derivatives have been shown to have advantageous immune properties in vitro, such observations could not be determined experimentally in vivo because of ethical and technical constraints. However, the generation of humanized mice (hu-mice) harboring a human immune system has provided a tool to perform in vivo immunologic studies of human cells and tissues. Using this model, we sought to examine the therapeutic potential of hESC-derived endothelial cells, human embryonic fibroblasts, and cord blood-derived endothelial progenitor cells in a human immune system environment. Approach and Results-All cell types transplanted in hu-mice showed significantly reduced cell survival during the first 14 days post-transplantation compared with that observed in immunodeficient mice. During this period, no observable therapeutic effects were detected in the hindlimb ischemic mouse models. After this point, the cells demonstrated improved survival and contributed to a long-term improvement in blood perfusion. All cell types showed reduced therapeutic efficacy in hu-mice compared with NOD scid IL2 receptor gamma chain knockout mice. Interestingly, the eventual improvement in blood flow caused by the hESC-derived endothelial cells in hu-mice was not much lower than that observed in NOD scid IL2 receptor gamma chain knockout mice. Conclusions-These findings suggest that hESC derivatives may be considered a good source for cell therapy and that humice could be used as a preclinical in vivo animal model for the evaluation of therapeutic efficacy to predict the outcomes of human clinical trials. Therapeutic Efficacy of Human Embryonic Stem Cell-Derived Endothelial Cells in Humanized Mouse Models Harboring a Human Immune SystemHeung-Mo Yang,* Sung-Hwan Moon,* Young-Sil Choi, Soon-Jung Park, Yong-Soo Lee, Hyun-Joo Lee, Sung-Joo Kim, † Hyung-Min Chung † However, because of obvious physiological differences between mice and humans, such models do not necessarily represent outcomes in humans. 12 To provide more suitable in vivo models, mice have been humanized to recreate complex human physiological processes in small animals through the transplantation of functional human tissues into immunodeficient mice.13 Different models of humanized mice (humice) have been generated for various types of biomedical research, such as studies of cancer, hematology, and HIV/ AIDS. [14][15][16] In particular, the technology for creating hu-mice harboring human immune systems has advanced in recent years and now permits the long-term engraftment of human hematopoietic stem cells and the production of hematopoietic lineages, including B and T cells. 13,17 This type of hu-mouse model is thought to provide a useful preclinical model to test the safety and efficacy of hESC-based regenerative medicine. 18The potential therapeutic application of hESC-derived endothel...

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Human Cord Blood-Derived Endothelial Progenitor Cells and Their Conditioned Media Exhibit Therapeutic Equivalence for Diabetic Wound Healing

Cited by 102 publications

References 27 publications

Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice

Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice

Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells

Therapeutic Efficacy of Human Embryonic Stem Cell–Derived Endothelial Cells in Humanized Mouse Models Harboring a Human Immune System

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