Soluble factors derived from human amniotic epithelial cells suppress collagen production in human hepatic stellate cells

Hodge, Alexander; Lourensz, Dinushka; Vaghjiani, Vijesh; Nguyên, Hoàng; Tchongue, Jorge; Wang, Bo; Murthi, Padma; Sievert, William; Manuelpillai, Ursula

doi:10.1016/j.jcyt.2014.01.005

Cited by 55 publications

(60 citation statements)

References 60 publications

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“…Previous studies have demonstrated the therapeutic potential of hAECs in various tissue repairs, including lung injury [10, 11, 14], brain injury [20], myocardial infarction [21], kidney injury [22], and liver fibrosis [23, 24]. Nonetheless, the therapeutic effect of hAECs on diabetic wound healing is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization

Zheng

Fan

et al. 2018

Stem Cells International

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Human amniotic epithelial cells (hAECs) are nontumorigenic, highly abundant, and low immunogenic and possess multipotent differentiation ability, which make them become ideal alternative stem cell source for regenerative medicine. Previous studies have demonstrated the therapeutic potential of hAECs in many tissue repairs. However, the therapeutic effect of hAECs on diabetic wound healing is still unknown. In this study, we injected hAECs intradermally around the full-thickness excisional skin wounds of db/db mice and found that hAECs significantly accelerated diabetic wound healing and granulation tissue formation. To explore the underlying mechanisms, we measured inflammation and neovascularization in diabetic wounds. hAECs could modulate macrophage phenotype toward M2 macrophage, promote switch from proinflammatory status to prohealing status of wounds, and increase capillary density in diabetic wounds. Furthermore, we found that the hAEC-conditioned medium promoted macrophage polarization toward M2 phenotype and facilitated migration, proliferation, and tube formation of endothelial cells through in vitro experiments. Taken together, we first reported that hAECs could promote diabetic wound healing, at least partially, through paracrine effects to regulate inflammation and promote neovascularization.

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Section: Discussionmentioning

confidence: 99%

Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization

Zheng

Fan

et al. 2018

Stem Cells International

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“…Importantly, hAECs demonstrate anti‐inflammatory, anti‐fibrotic, and immunomodulatory properties in vitro and in vivo . We have shown that hAEC‐derived soluble factors demonstrated similar benefits suggesting that secreted factors may be as efficacious as whole cells . While we have demonstrated anti‐inflammatory and anti‐fibrotic effects in models of lung injury and a toxin‐induced model of liver fibrosis, hAECs have not been investigated in NAFLD and NASH.…”

Section: Introductionmentioning

confidence: 90%

Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non‐alcoholic steatohepatitis

Kuk

Hodge

Sun

et al. 2019

J of Gastro and Hepatol

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Background and Aim Non‐alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. Currently, lifestyle modification is the only effective treatment. We have shown that human amnion epithelial cells (hAECs) reduce inflammation and fibrosis in toxin‐induced liver injury models. We examined the effect of these cells and the soluble factors released by the cells into culture medium (hAEC conditioned medium [hAEC‐CM]) in a diet‐induced murine NASH model. Methods C57BL/6J male mice received a Western “fast food diet” for 42 weeks. Group 1 received an intraperitoneal injection of 2 × 106 hAECs at week 34, group 2 received an additional hAEC dose at week 38, and group 3 received thrice weekly hAEC‐CM injections intraperitoneal for 8 weeks from week 34. Liver fibrosis area, inflammation, and fibrosis regulators were measured by immunohistochemistry, qPCR, and gelatin zymography. Metabolic parameters were also assessed. Results Fast food diet‐fed mice demonstrated peri‐cellular hepatic fibrosis, inflammation, and steatosis typical of NASH. Liver fibrosis area was reduced by 40% in hAEC‐treated and hAEC‐CM‐treated mice. hAEC treatment significantly reduced pSMAD 2/3 signaling and the number of activated hepatic stellate cells and liver macrophages. Matrix metalloproteinase 2 and 9 gene and protein expression were variably affected. hAEC treatment did not alter the NASH activity score or metabolic parameters such as bodyweight, total cholesterol, or glucose tolerance. Conclusion Human amnion epithelial cell and hAEC‐CM significantly reduced hepatic inflammation and fibrosis in a diet‐induced non‐alcoholic fatty liver disease model. Although hAEC and hAEC‐CM did not affect the metabolic components of NASH, their therapeutic potential is promising and warrants further investigation.

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“…The anti‐fibrotic actions of placental‐derived stem cells including those derived from the fetal membranes have been compared in a mouse model of bleomycin‐induced lung fibrosis . This study showed that allogeneic and xenogeneic fetal membrane derived stem cells were similarly efficacious in reducing neutrophil infiltration and fibrosis associated with bleomycin instillation .…”

Section: Preclinical Applicationsmentioning

confidence: 99%

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Lim

2017

Stem Cells Translational Medicine

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The clinical application of the fetal membranes dates back to nearly a century. Their use has ranged from superficial skin dressings to surgical wound closure. The applications of the fetal membranes are constantly evolving, and key to this is the uncovering of multiple populations of stem and stem‐like cells, each with unique properties that can be exploited for regenerative medicine. In addition to pro‐angiogenic and immunomodulatory properties of the stem and stem‐like cells arising from the fetal membranes, the dehydrated and/or decellularized forms of the fetal membranes have been used to support the growth and function of other cells and tissues, including adipose‐derived mesenchymal stem cells. This concise review explores the biological origin of the fetal membranes, a history of their use in medicine, and recent developments in the use of fetal membranes and their derived stem and stem‐like cells in regenerative medicine. Stem Cells Translational Medicine 2017;6:1767–1776

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Soluble factors derived from human amniotic epithelial cells suppress collagen production in human hepatic stellate cells

Cited by 55 publications

References 60 publications

Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization

Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating Inflammation and Promoting Neovascularization

Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non‐alcoholic steatohepatitis

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

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