TABLE 3.
Summary of studies based on AME.
| Author, year | Therapeutic goal | Experimental settings | Target tissue/cells | Conclusion | References |
| Chang, 2002 | Inflammatory skin diseases | In vitro | HaCaT cells | AME can be utilized to treat inflammatory skin diseases such as UV-induced skin diseases as it decreases the induction of iNOS mRNA and generation of NO in HaCaT cell by UVB radiation and can protect cells from death or morphological alteration | Chang et al., 2002 |
| Li, 2008 | Stem cell preservation and expansion | In vitro | AMSCs | AME like AM has the potential to help AMSCs maintain their progenitor status and can reverse differentiated myofibroblasts to a fibroblast phenotype | Li et al., 2008 |
| He, 2008 | Anti-inflammatory agent | In vitro | RAW 264.7 cells | AME retains anti-inflammatory activities and does so by downregulating activation and inducing apoptosis in macrophages | He et al., 2008 |
| He, 2009 | Ocular surface reconstruction | In vitro | Human corneal fibroblasts, RAW 264.7 cells | The HC-HA complex is an active component in AM responsible for the suppression of TGF-β1 promoter activity, linkable to its anti-scarring and anti-inflammatory effect | He et al., 2009 |
| Sheha, 2010 | Chemical ocular burn | Non-comparative interventional case series | Human eyes | Addition of AME to the standard treatment of mild-to-moderate cases of acute chemical burns results in a reduction of pain, haze, and inflammation and promotes epithelialization | Sheha et al., 2010 |
| Choi, 2013 | Wound healing | In vivo | Sprague Dawley rats | In comparison with the commercial product, the double-layered AME-loaded wound dressing enhanced wound healing | Choi et al., 2014 |
| Xiao, 2013 | Dry eye | In vivo | BALB/c mouse | Topical application of AME on BAC-induced dry eye resulted in improved clinical symptoms of dry eye, reduced corneal inflammation, decreased squamous metaplasia, protected corneal epithelial cells and increased their proliferation, and increased the density of goblet cells | Xiao et al., 2013 |
| Kang, 2013 | Wound healing | In vitro and in vivo | Primary human foreskin fibroblasts New Zealand white rabbit | Intradermal injections of AME fluid on wound sites resulted in increased wound closure rate and promoted epidermal and dermal regeneration without causing undesirable hyperproliferation of damaged tissue | Kang et al., 2013 |
| Mahbod, 2014 | HGF content of AME | In vitro | – | The extraction method of AME and its storing conditions has a direct influence on its extractable components. | Mahbod et al., 2014 |
| Tauzin, 2014 | Chronic leg ulcers | In vitro | Normal and ulcer fibroblasts | Although AME is beneficial in leg ulcer treatment clinically, in this study, it barely stimulated ulcer fibroblasts | Tauzin et al., 2014 |
| Dudok, 2014 | Corneal surface injuries | In vitro | Human corneal epithelial and limbal cells | HCE cells healed faster after mechanical injury when they were cultured with AME | Dudok et al., 2015 |
| Lee, 2016 | Ocular surface disorders | In vitro | Human corneal epithelial cells | Homogenized AME of less than 3 kDa had a higher capacity in the reduction of inflammation | Lee et al., 2016 |
| Vojdani, 2016 | Stem cell therapy | In vitro | HUCBMSC | AME has the potential to enhance the proliferation capacity of HUCBMSCs without influencing their morphology and differentiation capacity | Vojdani et al., 2016 |
| Go, 2016 | osteogenic effects | In vitro | MG-63 | Unlike CME, the EGF content of AME negatively regulated the osteogenic differentiation of MG-63 cells. However, it can be modified with EGFR inhibitors to modulate the bone density or calcification during bone regeneration | Go et al., 2016 |
| Yadav, 2017 | The antibacterial effect of AME against S. pneumonia | In vitro and in vivo | Microtiter plate assay and OM rat model | AME/CME contains essential antimicrobial proteins and peptides to inhibit S. pneumoniae growth in both planktonic and biofilm states | Yadav et al., 2017 |
| Litwiniuk, 2017 | Cell growth | In vitro | HaCaT, Wi-38, HECa-10 | The placental portion of AM stimulates both fibroblasts and keratinocytes and is best suited for applications related to wound healing. On the other hand, the cervical portion of AM provide from C-section is a better option for the treatment of ocular diseases as it stimulates epithelialization | Brown et al., 1989 |
| Baradaran-rafii, 2017 | LSC transplantation | In vivo | Human eyes | Application of AM as a supporter (niche/scaffold) and AMEED as the promoter of limbal/epithelial cell growth may be a promising surgical procedure for LSC cultivation | Baradaran-Rafii et al., 2018 |
| Laranjeira, 2018 | Allergic disorders | In vitro | Human PBMCs | AME induces anti-inflammatory effect on T cells | Laranjeira et al., 2018 |
| Motlagh, 2018 | Stem cell therapy | In vitro | Decidual MSCs | Coatings based on AME maintain or reduce the size of DMSCs and promote their proliferation, osteogenic, and adipogenic differentiation | Shakouri-Motlagh et al., 2019 |
| Faridvand, 2018 | Myocardial hypoxia injury | In vitro | H9c2 cardiomyocytes | Proteins present in AME have cardioprotective effects in hypoxic conditions by reducing oxidative stress and inflammatory response and modulating apoptosis | Faridvand et al., 2018 |
| Farzan, 2018 | Wound healing | In vivo | Rat skin | AME as well as deferoxamine has the potential to induce angiogenesis during wound healing | Farzan et al., 2018 |
| Asl, 2019 | Corneal surgery and cell therapy | Ex vivo and in vivo | LSCs and rabbit | AMEED enhances LSC proliferation and decreases epithelium healing duration by 1 day in comparison to the control group | Asl et al., 2019 |
| Fardivand, 2019 | Myocardial hypoxia injury | In vitro | H9c2 | AME proteins protect cardiomyocytes in hypoxic conditions through the regulation of HO-1 by Nrf2 activation | Faridvand et al., 2019 |
| Fardivand, 2020 | Cardiotoxicity | In vitro | H9c2 | AME has the potential to suppress the cardiotoxicity induced by DOX through inhibition of apoptosis and oxidative stress | Faridvand et al., 2020 |
| Liu, 2020 | Dry eye disease | In vitro | Human corneal epithelial cells | Through the upregulation of MMP-8 and downregulation of IL-1β and TNF-α, AME protects corneal epithelial cells against benzalkonium chloride | Liu et al., 2020 |
| Park, 2020 | OM | In vitro | ME mucosa of rats | Possibly AME exerts anti-proliferative and anti-inflammatory effects on infected ME mucosa | Park et al., 2020 |
| Shabani, 2020 | Ocular surface disease | In vitro | HUVECs | AME loaded chitosan-dextran sulfate nanoparticles decreased the proliferation of endothelial cells | Shabani et al., 2020 |