Human Amnion-Derived Stem Cells Have Immunosuppressive Properties on NK Cells and Monocytes

Li, Jiali; Koike-Soko, Chika; Sugimoto, Jun; Yoshida, Toshiko; Okabe, Motonori; Nikaido, Toshio

doi:10.3727/096368914x685230

Cited by 50 publications

(55 citation statements)

References 56 publications

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“…Although it has previously been reported that hAMTCs act directly on monocytes (Magatti et al , ) and that amniotic‐derived cells decrease the production of TNF α and IL‐6 cytokines in LPS‐stimulated monocytes (Li et al , ), we here provided the first evidence that hAMTCs and their CM induce macrophage differentiation in the promonocytic U937 cell line or peripheral blood monocytes, in the absence of any other exogenous agents. Importantly, we demonstrated that hAMTCs or their CM favour the generation of macrophages with M2‐like features, even in a M1‐conditioned environment, consequently affecting their functions, such as higher phagocytosis.…”

Section: Discussionmentioning

confidence: 43%

“…We found that CM obtained from hAMSC culture affects both central and effector memory T lymphocyte subsets, significantly reduces the expression of markers associated with Th1 and Th17 populations and significantly induces the regulatory T cells compartment (Pianta et al , ). Furthermore, not only T lymphocytes but also the in vitro proliferation of B cells (Li et al , ), the cytotoxicity of natural killer cells (Li et al , ) and the migration of neutrophils and macrophages (Li et al , ; Tan et al , ) have been shown to be affected by amniotic cells and their CM. Moreover, we and others have demonstrated that amniotic cells and their CM impair the development of dendritic cells from primary monocytes (Magatti et al , ; Kronsteiner et al , ; Banas et al , ; Magatti et al , ).…”

Section: Introductionmentioning

confidence: 99%

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Human amnion favours tissue repair by inducing the M1-to-M2 switch and enhancing M2 macrophage features

Magatti

Vertua

Munari

et al. 2016

J Tissue Eng Regen Med

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Human amniotic mesenchymal cells (hAMTCs) possess interesting immunomodulatory properties, making them attractive candidates for regenerative medicine applications. Recent in vivo reports argue in favour of an important role for macrophages as targets of hAMTC‐mediated suppression of inflammation and the enhancement of tissue repair. However, a comprehensive study of the effects of hAMTCs and their conditioned medium (CM) on human macrophage differentiation and function is unavailable. In the present study we found that hAMTCs and CM induce the differentiation of myeloid cells (U937 and monocytes) towards macrophages. We then investigated their effects on monocytes differentiated toward pro‐inflammatory M1 and anti‐inflammatory M2 macrophages. Monocytes treated under M1 conditions in the presence of hAMTCs or CMs shifted towards M2‐like macrophages, which expressed CD14, CD209, CD23, CD163 and PM‐2 K, possessed higher phagocytic activity and produced higher IL‐10 and lower pro‐inflammatory cytokines. They were also poor T cell stimulators and Th1 inducers, while they were able to increase activated and naïve suppressive Treg subsets. We show that prostaglandins, and not IL‐6, play a role in determining the M2 activation status. Instead, monocytes treated under M2 conditions in the presence of hAMTCs or CM retained M2‐like features, but with an enhanced anti‐inflammatory profile, having a reduced expression of the co‐stimulatory molecule CD80, reduced phagocytosis activity and decreased the secretion of inflammatory chemokines. Importantly, we provide evidence that macrophages re‐educated by CM improve tissue regeneration/repair in wound‐healing models. In conclusion, we identified new cell targets of hAMTCs and their bioactive factors and here provide insight into the beneficial effects observed when these cells are used in therapeutic approaches in vivo. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

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Section: Discussionmentioning

confidence: 43%

Section: Introductionmentioning

confidence: 99%

Human amnion favours tissue repair by inducing the M1-to-M2 switch and enhancing M2 macrophage features

Magatti

Vertua

Munari

et al. 2016

J Tissue Eng Regen Med

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“…A study demonstrated that both hAECs and AMSC express IL‐4, IL‐6, IL‐8, HLA‐G and TGF‐β. IL‐10 and cyclooxygenase expressions were upregulated upon IL‐1β stimulation or co‐culturing with NK cells . These data indicate that hAEC‐derived cytokines also modulate NK cell activity.…”

Section: Immunomodulatory Properties Of Amniotic Epithelial Cellsmentioning

confidence: 74%

Stem cell characteristics and the therapeutic potential of amniotic epithelial cells

Miki

2018

American J Rep Immunol

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Multiple stem cell types can be isolated from the human placenta. Recent advances in stem cell biology have revealed that human amniotic epithelial cells (hAECs) are one of the perinatal stem cells which possess embryonic stem cell-like differentiation capability and adult stem cell-like immunomodulatory properties. Unlike other types of placental stem cells, hAECs are derived from pluripotent epiblasts and maintain multilineage differentiation potential throughout gestation. Similar to mesenchymal stem cells, hAECs are also able to modulate the local immune response. These, and other properties, make hAECs attractive for cellular therapy. This review article summarizes current knowledge of stem cell characteristics and immunomodulatory properties of amniotic epithelial cells and aims to advance our understanding towards the goal of novel therapy development.

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“…In line with a rapid transition from the inflammatory to the reparative phase (Manuelpillai et al, ) was the evidence of the increased local expression of M2Mφ‐associated genes and the lower IL12b:IL10 ratio recorded in the presence of hAECs. This suggested an Mφ skewing towards M2 phenotype, along with simultaneous higher expression of IL10, essential to prevent the production of proinflammatory cells or factors (Li et al, ). The cytokine expression profile is specular in CTR: Here, the prevalence of proinflammatory M1Mφ markers (CD68) and the local presence of ongoing inflammatory molecules (high concentration of IL12b mRNA) persisted over 28 days probably leading to a spontaneous fibrotic scar evolution.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of hAECs for early Achilles tendon defect repair through regeneration

Barboni

Russo

Gatta

et al. 2017

J Tissue Eng Regen Med

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Cell-based therapy holds great promise for tendon disorders, a widespread debilitating musculoskeletal condition. Even if the cell line remains to be defined, preliminary evidences have proven that amniotic-derived cells possess in vitro and in vivo a great tenogenic potential. This study investigated the efficacy of transplanted human amniotic epithelial cells (hAECs) by testing their early regenerative properties and mechanisms involved on a validated ovine Achilles tendon partial defect performed on 29 animals. The injured tendons treated with hAECs recovered rapidly, in 28 days, structural and biomechanical properties undertaking a programmed tissue regeneration, differently from the spontaneous healing tissues. hAECs remained viable within the host tendons establishing with the endogenous progenitor cells an active dialogue. Through the secretion of modulatory factors, hAECs inhibited the inflammatory cells infiltration, activated the M2 macrophage subpopulation early recruitment, and accelerated blood vessel as well as extracellular matrix remodelling. In parallel, some in situ differentiated hAECs displayed a tenocytelike phenotype. Both paracrine and direct hAECs stimulatory effects were confirmed analysing their genome profile before and after transplantation. The 49 human up-regulated transcripts recorded in transplanted hAECs belonged to tendon lineage differentiation (epithelial-mesenchymal transition, connective specific matrix components, and skeleton or muscle system development-related transcripts), as well as the in situ activation of paracrine signalling involved in inflammatory and immunomodulatory response. Altogether, these evidences support the hypothesis that hAECs are a practicable and efficient strategy for the acute treatment of tendinopathy, reinforcing the idea of a concrete use of amniotic epithelial cells towards the clinical practice.

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Human Amnion-Derived Stem Cells Have Immunosuppressive Properties on NK Cells and Monocytes

Cited by 50 publications

References 56 publications

Human amnion favours tissue repair by inducing the M1-to-M2 switch and enhancing M2 macrophage features

Human amnion favours tissue repair by inducing the M1-to-M2 switch and enhancing M2 macrophage features

Stem cell characteristics and the therapeutic potential of amniotic epithelial cells

Therapeutic potential of hAECs for early Achilles tendon defect repair through regeneration

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