Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1β and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage

Liang, Hongsheng; Dong, Guan; Gao, Aili; Yin, Yibo; Meng, Jing; Yang, Lin; Ma, Wei; Hu, Enxi; Zhang, Xiangtong

doi:10.1016/j.jcyt.2013.11.007

Cited by 18 publications

(13 citation statements)

References 54 publications

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“…These immunomodulatory properties have laid the foundation for the use of these cells in treating inflammatory and immune-based diseases, and encouraging results have been obtained in different disease models (Table 4 ). In ischemic stroke, hAEC transplantation significantly reduced inflammation, leading to the recovery of brain function [ 70 ] and the improvement of brain function after intracerebral hemorrhage (ICH) by reducing microglial activation and producing anti-inflammatory factors [ 101 ]. In perinatal brain injury, hAEC transplantation reduced apoptosis and astrocyte areal coverage in the white matter, and increased the density of total and activated microglia via the release of trophic factors [ 102 ].…”

Section: Methodsmentioning

confidence: 99%

Application of human amniotic epithelial cells in regenerative medicine: a systematic review

Zhang

Lai

2020

Stem Cell Res Ther

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Human amniotic epithelial cells (hAECs) derived from placental tissues have gained considerable attention in the field of regenerative medicine. hAECs possess embryonic stem cell-like proliferation and differentiation capabilities, and adult stem cell-like immunomodulatory properties. Compared with other types of stem cell, hAECs have special advantages, including easy isolation, plentiful numbers, the obviation of ethical debates, and non-immunogenic and non-tumorigenic properties. During the past two decades, the therapeutic potential of hAECs for treatment of various diseases has been extensively investigated. Accumulating evidence has demonstrated that hAEC transplantation helps to repair and rebuild the function of damaged tissues and organs by different molecular mechanisms. This systematic review focused on summarizing the biological characteristics of hAECs, therapeutic applications, and recent advances in treating various tissue injuries and disorders. Relevant studies published in English from 2000 to 2020 describing the role of hAECs in diseases and phenotypes were comprehensively sought out using PubMed, MEDLINE, and Google Scholar. According to the research content, we described the major hAEC characteristics, including induced differentiation plasticity, homing and differentiation, paracrine function, and immunomodulatory properties. We also summarized the current status of clinical research and discussed the prospects of hAEC-based transplantation therapies. In this review, we provide a comprehensive understanding of the therapeutic potential of hAECs, including their use for cell replacement therapy as well as secreted cytokine and exosome biotherapy. Moreover, we showed that the powerful immune-regulatory function of hAECs reveals even more possibilities for their application in the treatment of immune-related diseases. In the future, establishing the optimal culture procedure, achieving precise and accurate treatment, and enhancing the therapeutic potential by utilizing appropriate preconditioning and/or biomaterials would be new challenges for further investigation.

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Section: Methodsmentioning

confidence: 99%

Application of human amniotic epithelial cells in regenerative medicine: a systematic review

Zhang

Lai

2020

Stem Cell Res Ther

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“…Hyperglycemia also drives the inflammatory infiltration of macrophages in the DRG, which subsequently contributes to nerve demyelination and release of different proinflammatory mediators having an important role in the pathogenesis of painful neuropathy (14,84,85). Macrophage-derived proinflammatory cytokines, such as TNF-␣, IL-1␤, and IL-6, are documented to contribute to the pathogenesis of painful diabetic neuropathy (86,87). In the current study, Pdk2/4 deficiency markedly attenuated the diabetes-induced macrophage infiltration and the subsequent expression of proinflammatory cytokines in the DRG.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy

Rahman

Jha

Kim

et al. 2016

Journal of Biological Chemistry

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The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy. Streptozotocin-induced diabetes substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of Pdk2 and Pdk4 attenuated the hyperglycemia-induced pain hypersensitivity. Mechanistically, Pdk2/4 deficiency inhibited the diabetes-induced lactate surge, expression of pain-related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which probably accounts for the attenuated pain hypersensitivity. Pdk2/4-deficient mice were partly resistant to the diabetes-induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, lactic acid treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or lactic acid production substantially attenuated diabetes-induced pain hypersensitivity. Taken together, PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic DRG, thereby contributing to the pathogenesis of painful diabetic neuropathy.Painful neuropathy is one of the most common complications of diabetes. Patients with diabetes frequently exhibit a variety of aberrant sensations, including pain hypersensitivity (1, 2). Interrelation and mutual perpetuation of distinct aberrations of specific metabolic pathways cause painful diabetic neuropathy. Furthermore, painful diabetic neuropathy probably results from a combination of metabolic and immune factors (3, 4). Metabolic aberrations are thought to be early events in painful diabetic neuropathy, leading to biochemical, structural, and functional changes in the dorsal root ganglion (DRG) 3 and its nerve trunk (5, 6). Likewise, hyperglycemia-induced immune activation creates an inflammatory microenvironment surrounding the influenced nerves (7).The DRG is pathologically important in diabetes presenting with painful neuropathic states, which patients with early polyneuropathy commonly experience (8). Ganglionic sensory neurons are devoid of any special protection by the blood-brain or blood-nerve barrier and have higher metabolic requirements than the nerve trunk, which makes the ganglion a vulnerable site in the pathogenesis of diabetic neurop...

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“…In ICH animal models, hAEC grafts could enhance neural cell survival and regeneration in the perifocal tissue [14, 25]. Moreover, activated microglia were suppressed in the perihematoma regions, and inflammatory factor levels of TNF- α , IL-1 β , and MMP-12 were reduced, which might be attributed to the reduced extent of brain edema and neurological deficits [14, 36]. Taken together, preclinical studies suggest that hAEC therapy may be effective in the treatment of ischemic stroke and ICH by the following potential mechanism.…”

Section: Prospective Applications Of Haecsmentioning

confidence: 99%

“…Second, hAECs could suppress the inflammatory response by inhibiting the activation of microglial cells and producing anti-inflammatory factors and immunosuppressive factors, which contribute to the protection of neurons from immune cell-mediated apoptosis. Third, hAECs could secrete necessary cytokines, NTFs, and growth factors, which provide a favourable microenvironment for the survival and regeneration of neural cells and synaptogenesis, eventually contributing to the reinnervation of lost connections and restoring cellular function [36–40]. Finally, systemically administered hAECs could attenuate poststroke immunosuppression, attributable to the lower extent of infection and beneficial for overall recovery and brain repair processes.…”

Section: Prospective Applications Of Haecsmentioning

confidence: 99%

Therapeutic Potential of Human Amniotic Epithelial Cells on Injuries and Disorders in the Central Nervous System

Zhang

Tsang

et al. 2019

Stem Cells International

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Despite recent advances in neurosurgery and pharmaceuticals, contemporary treatments are ineffective in restoring lost neurological functions in patients with injuries and disorders of the central nervous system (CNS). Therefore, novel and effective therapies are urgently needed. Recent studies have indicated that stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), could repair/replace damaged or degenerative neurons and improve functional recovery in both preclinical and clinical trials. However, there are many unanswered questions and unsolved issues regarding stem cell therapy in terms of potency, stability, oncogenicity, immune response, cell sources, and ethics. Currently, human amniotic epithelial cells (hAECs) derived from the amnion exhibit considerable advantages over other stem cells and have drawn much attention from researchers. hAECs are readily available, pose no ethical concerns, and have little risk of tumorigenicity and immunogenicity. Mounting evidence has shown that hAECs can promote neural cell survival and regeneration, repair affected neurons, and reestablish damaged neural connections. It is suggested that hAECs may be the most promising candidate for cell-based therapy of neurological diseases. In this review, we mainly focus on recent advances and potential applications of hAECs for treating various CNS injuries and neurodegenerative disorders. We also discuss current hurdles and challenges regarding hAEC therapies.

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Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1β and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage

Cited by 18 publications

References 54 publications

Application of human amniotic epithelial cells in regenerative medicine: a systematic review

Application of human amniotic epithelial cells in regenerative medicine: a systematic review

Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy

Therapeutic Potential of Human Amniotic Epithelial Cells on Injuries and Disorders in the Central Nervous System

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