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Keywords = human amniotic epithelial cell

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21 pages, 4743 KB  
Article
Transcriptomic Investigation of FoxM1-Mediated Neuroprotection by hAEC-Derived Exosomes in an In Vitro Ischemic Stroke Model
by Dong Wang, Jiaxin Liu, Liang Wu, Xiubao Yang, Zhihao Fang, Zhong Sun and Dong Chen
Biology 2025, 14(10), 1368; https://doi.org/10.3390/biology14101368 - 7 Oct 2025
Abstract
Human amniotic epithelial cell-derived exosomes (hAECs-Exos) are nanoscale extracellular vesicles with neuroprotective, regenerative, and anti-inflammatory properties, presenting a promising cell-free therapeutic approach for ischemic stroke. This study investigated the protective effects of hAECs-Exos against ischemic injury and explored the underlying molecular mechanisms. An [...] Read more.
Human amniotic epithelial cell-derived exosomes (hAECs-Exos) are nanoscale extracellular vesicles with neuroprotective, regenerative, and anti-inflammatory properties, presenting a promising cell-free therapeutic approach for ischemic stroke. This study investigated the protective effects of hAECs-Exos against ischemic injury and explored the underlying molecular mechanisms. An optimized oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in murine hippocampal HT22 neurons and BV2 microglial cells to simulate ischemic conditions. hAECs-Exos were successfully isolated and characterized via transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Confocal microscopy confirmed efficient exosome uptake by both cell types. Functional analyses revealed that hAECs-Exos significantly improved cell viability, suppressed pro-inflammatory cytokine release, alleviated oxidative stress, and modulated apoptosis-related proteins. RNA sequencing identified Forkhead box protein M1 (FoxM1) as a significantly upregulated transcription factor following hAECs-Exos treatment. Further experiments demonstrated that knockdown of FoxM1 in hAECs abolished the beneficial effects of exosomes on the viability of HT22 and BV2 cells and on the suppression of inflammation, oxidative stress, and apoptosis. These findings indicate that hAECs-Exos confer neuroprotection through FoxM1-dependent mechanisms. Together, our results highlight the therapeutic potential of hAECs-Exos as a safe, effective, and clinically translatable strategy for ischemic stroke treatment, warranting future validation in vivo and rescue experiments to fully elucidate FoxM1’s causal role. Full article
(This article belongs to the Special Issue Young Researchers in Neuroscience)
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22 pages, 1555 KB  
Review
The Human Amniotic Membrane: A Rediscovered Tool to Improve Wound Healing in Oral Surgery
by Maurizio Sabbatini, Paolo Boffano, Martina Ferrillo, Mario Migliario and Filippo Renò
Int. J. Mol. Sci. 2025, 26(17), 8470; https://doi.org/10.3390/ijms26178470 - 31 Aug 2025
Viewed by 1166
Abstract
Wound healing in oral surgery is influenced by systemic conditions (aging, diabetes) and habits (smoking, alcoholism), which can hinder the natural regenerative capacity of the oral mucosa. The human amniotic membrane (hAM), long recognized for its wound-healing properties, has gained attention as a [...] Read more.
Wound healing in oral surgery is influenced by systemic conditions (aging, diabetes) and habits (smoking, alcoholism), which can hinder the natural regenerative capacity of the oral mucosa. The human amniotic membrane (hAM), long recognized for its wound-healing properties, has gained attention as a valuable biomaterial in regenerative dentistry. Its biological composition—including epithelial and mesenchymal stem cells, collagen, growth factors, cytokines, and proteins with anti-inflammatory and antimicrobial properties—supports anti-inflammatory, angiogenic, immunomodulatory, and pro-epithelializing effects. These elements work synergistically to enhance tissue repair, reduce scarring, and promote rapid healing. The hAM can be preserved through cryopreservation, dehydration, or freeze-drying, maintaining its structural and functional integrity for diverse clinical uses. In oral surgery, the hAM has been applied with significant success to surgical wound coverage, treatment of periodontal and bone defects, and implant site regeneration, as well as management of complex conditions like medication-related osteonecrosis of the jaw (MRONJ). Clinical studies and meta-analyses support its safety, efficacy, and adaptability. Despite its proven therapeutic benefits, the hAM remains underutilized in dentistry due to challenges related to its preparation and storage. This review aims to highlight its potential and encourage broader clinical adoption in regenerative oral surgical practices. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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16 pages, 1489 KB  
Review
Caspase-14-like Proteases: An Epidermal Caspase and Its Evolutionarily Ancient Relatives
by Leopold Eckhart, Attila Placido Sachslehner, Julia Steinbinder and Heinz Fischer
Biomolecules 2025, 15(7), 913; https://doi.org/10.3390/biom15070913 - 22 Jun 2025
Viewed by 841
Abstract
Caspases are a family of cysteine-dependent aspartate-directed proteases implicated in programmed cell death. Humans have eleven proteolytically active caspases, namely caspase-1 through -10 and caspase-14. The latter is expressed exclusively in epithelial cells and constitutively resides in its active form in the cornified [...] Read more.
Caspases are a family of cysteine-dependent aspartate-directed proteases implicated in programmed cell death. Humans have eleven proteolytically active caspases, namely caspase-1 through -10 and caspase-14. The latter is expressed exclusively in epithelial cells and constitutively resides in its active form in the cornified layer of the human epidermis. Molecular phylogenetics has revealed that caspase-14 belongs to a subfamily of caspases, which also includes caspase-15 and -16. The latter are evolutionarily more ancient than caspase-14 and have been lost in the phylogenetic lineage leading to humans. Here, we review the molecular properties, the species distributions, and the biological roles of caspase-14-like proteases in amniotes. In contrast to the prodomain-less caspase-14, caspase-15 contains a prodomain that is predicted to assume a pyrin fold, and caspase-16 features a prodomain with unique sequence similarity to the catalytic domain. Gene knockout in mice, evolutionary gene loss in aquatic mammals and the association of human CASP14 mutations with ichthyosis indicate that caspase-14 is associated with the barrier function of mammalian skin. Caspase-15 is able to induce apoptosis in cell culture, but its role in vivo and the role of caspase-16 are currently unknown. We propose directions for research to further characterize caspase-14-like proteases. Full article
(This article belongs to the Section Molecular Biophysics: Structure, Dynamics, and Function)
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15 pages, 3149 KB  
Article
The Role of Beta-Defensin 2 in Preventing Preterm Birth with Chorioamnionitis: Insights into Inflammatory Responses and Epithelial Barrier Protection
by Sangho Yun, Shin-Hae Kang, Jiwon Ryu, Kyoungseon Kim, Keun-Young Lee, Jae Jun Lee, Ji Young Hong and Ga-Hyun Son
Int. J. Mol. Sci. 2025, 26(5), 2127; https://doi.org/10.3390/ijms26052127 - 27 Feb 2025
Viewed by 1187
Abstract
Antimicrobial peptides, such as beta-defensin 2 (BD2), are vital in controlling infections and immune responses. In this study, we investigated the expression and role of BD2 in the amniotic membrane and human amniotic epithelial cells (hAECs) from patients with preterm birth and chorioamnionitis, [...] Read more.
Antimicrobial peptides, such as beta-defensin 2 (BD2), are vital in controlling infections and immune responses. In this study, we investigated the expression and role of BD2 in the amniotic membrane and human amniotic epithelial cells (hAECs) from patients with preterm birth and chorioamnionitis, focusing on its regulation of inflammatory cytokines and its protective effect on the epithelial barrier. Our results show increased BD2 expression in chorioamnionitis, and Lipopolysaccharide (LPS)-induced inflammation increased BD2 release from hAECs in a dose- and time-dependent manner. BD2 treatment effectively modulated the inflammatory response by reducing pro-inflammatory cytokines (IL-6, IL-1β) and enhancing the release of the anti-inflammatory cytokine IL-10. Additionally, BD2 helps preserve epithelial barrier integrity by restoring E-cadherin expression and reducing Snail expression in inflamed hAECs. In an LPS-induced preterm birth mouse model, BD2 treatment delayed preterm delivery and reduced inflammatory cytokine levels. These results suggest that BD2 plays a protective role in preventing preterm birth by regulating inflammation and maintaining epithelial barrier function, highlighting its therapeutic potential for inflammation-related preterm birth. Full article
(This article belongs to the Special Issue Antimicrobial Peptides in Reproductive Health and Disease)
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17 pages, 2996 KB  
Article
Influence of the Surface Topography of Titanium Dental Implants on the Behavior of Human Amniotic Stem Cells
by Rodrigo Riedel, Soledad Pérez-Amodio, Laura Cabo-Zabala, Eugenio Velasco-Ortega, Julieta Maymó, Javier Gil, Loreto Monsalve-Guil, Iván Ortiz-Garcia, Antonio Pérez-Pérez, Victor Sánchez-Margalet and Alvaro Jiménez-Guerra
Int. J. Mol. Sci. 2024, 25(13), 7416; https://doi.org/10.3390/ijms25137416 - 6 Jul 2024
Cited by 3 | Viewed by 2215
Abstract
The dental implant surface plays a crucial role in osseointegration. The topography and physicochemical properties will affect the cellular functions. In this research, four distinct titanium surfaces have been studied: machined acting (MACH), acid etched (AE), grit blasting (GBLAST), and a combination of [...] Read more.
The dental implant surface plays a crucial role in osseointegration. The topography and physicochemical properties will affect the cellular functions. In this research, four distinct titanium surfaces have been studied: machined acting (MACH), acid etched (AE), grit blasting (GBLAST), and a combination of grit blasting and subsequent acid etching (GBLAST + AE). Human amniotic mesenchymal (hAMSCs) and epithelial stem cells (hAECs) isolated from the amniotic membrane have attractive stem-cell properties. They were cultured on titanium surfaces to analyze their impact on biological behavior. The surface roughness, microhardness, wettability, and surface energy were analyzed using interferometric microscopy, Vickers indentation, and drop-sessile techniques. The GBLAST and GBLAST + AE surfaces showed higher roughness, reduced hydrophilicity, and lower surface energy with significant differences. Increased microhardness values for GBLAST and GBLAST + AE implants were attributed to surface compression. Cell viability was higher for hAMSCs, particularly on GBLAST and GBLAST + AE surfaces. Alkaline phosphatase activity enhanced in hAMSCs cultured on GBLAST and GBLAST + AE surfaces, while hAECs showed no mineralization signals. Osteogenic gene expression was upregulated in hAMSCs on GBLAST surfaces. Moreover, α2 and β1 integrin expression enhanced in hAMSCs, suggesting a surface−integrin interaction. Consequently, hAMSCs would tend toward osteoblastic differentiation on grit-blasted surfaces conducive to osseointegration, a phenomenon not observed in hAECs. Full article
(This article belongs to the Collection Feature Papers in Materials Science)
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17 pages, 3794 KB  
Article
Stretch Causes cffDNA and HMGB1-Mediated Inflammation and Cellular Stress in Human Fetal Membranes
by Justin Gary Padron, Chelsea A. Saito Reis, Po’okela K. Ng, Nainoa D. Norman Ing, Hannah Baker, Kamalei Davis, Courtney Kurashima and Claire E. Kendal-Wright
Int. J. Mol. Sci. 2024, 25(10), 5161; https://doi.org/10.3390/ijms25105161 - 9 May 2024
Viewed by 1430
Abstract
Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of [...] Read more.
Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of parturition by influencing cellular stress mechanisms that make the fetal membranes (FMs) more susceptible to rupture. DAMPs induce inflammation in many different tissue types. Indeed, they precipitate the subsequent release of several proinflammatory cytokines that are known to be key for the weakening of FMs. Previously, we have shown that in vitro stretch of human amnion epithelial cells (hAECs) induces a cellular stress response that increases high-mobility group box-1 (HMGB1) secretion. We have also shown that cell-free fetal DNA (cffDNA) induces a cytokine response in FM explants that is fetal sex-specific. Therefore, the aim of this work was to further investigate the link between stretch and the DAMPs HMGB1 and cffDNA in the FM. These data show that stretch increases the level of cffDNA released from hAECs. It also confirms the importance of the sex of the fetus by demonstrating that female cffDNA induced more cellular stress than male fetuses. Our data treating hAECs and human amnion mesenchymal cells with HMGB1 show that it has a differential effect on the ability of the cells of the amnion to upregulate the proinflammatory cytokines and propagate a proinflammatory signal through the FM that may weaken it. Finally, our data show that sulforaphane (SFN), a potent activator of Nrf2, is able to mitigate the proinflammatory effects of stretch by decreasing the levels of HMGB1 release and ROS generation after stretch and modulating the increase of key cytokines after cell stress. HMGB1 and cffDNA are two of the few DAMPs that are known to induce cytokine release and matrix metalloproteinase (MMP) activation in the FMs; thus, these data support the general thesis that they can function as potential central players in the normal mechanisms of FM weakening during the normal distension of this tissue at the end of a normal pregnancy. Full article
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21 pages, 7137 KB  
Article
Comparison of the Efficacy of Two Routes of Administration of Human Amniotic Epithelial Cells in Cell Therapy of Acute Hepatic Insufficiency
by Patrycja Wieczorek, Piotr Czekaj, Mateusz Król, Edyta Bogunia, Mateusz Hermyt, Emanuel Kolanko, Jakub Toczek, Aleksandra Skubis-Sikora, Aniela Grajoszek and Rafał Stojko
Pharmaceuticals 2024, 17(4), 476; https://doi.org/10.3390/ph17040476 - 8 Apr 2024
Viewed by 1709
Abstract
The route of administration of implanted cells may affect the outcome of cell therapy by directing cell migration to the damaged site. However, the question of the relationship between the route of administration, the efficacy of colonisation of a given organ, and the [...] Read more.
The route of administration of implanted cells may affect the outcome of cell therapy by directing cell migration to the damaged site. However, the question of the relationship between the route of administration, the efficacy of colonisation of a given organ, and the efficacy of cell therapy has not been resolved. The aim of the study was to localise transplanted intravenously and intraperitoneally human amniotic epithelial cells (hAECs) in the tissues of mice, both healthy and injured, in an animal experimental model of acute liver failure (ALF). Mice intoxicated with D-Galactosamine (D-GalN) at a dose of 150 mg/100 g body weight received D-GalN alone or with a single dose of hAECs administered by different routes. Subsequently, at 6, 24, and 72 h after D-GaIN administration and at 3, 21, and 69 h after hAEC administration, lungs, spleen, liver, and blood were collected from recipient mice. The degree of liver damage and regeneration was assessed based on biochemical blood parameters, histopathological evaluation (H&E staining), and immunodetection of proliferating (Ki67+) and apoptotic (Casp+) cells. The biodistribution of the administered cells was based on immunohistochemistry and the identification of human DNA. It has been shown that after intravenous administration, in both healthy and intoxicated mice, most of the transplanted hAECs were found in the lungs, while after intraperitoneal administration, they were found in the liver. We concluded that a large number of hAECs implanted in the lungs following intravenous administration can exert a therapeutic effect on the damaged liver, while the regenerative effect of intraperitoneally injected hAECs on the liver was very limited due to the relatively lower efficiency of cell engraftment. Full article
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18 pages, 2161 KB  
Review
Amniotic Membrane and Its Derivatives: Novel Therapeutic Modalities in Liver Disorders
by Mandana Kazem Arki, Kasra Moeinabadi-Bidgoli, Nikoo Hossein-Khannazer, Roberto Gramignoli, Mustapha Najimi and Massoud Vosough
Cells 2023, 12(16), 2114; https://doi.org/10.3390/cells12162114 - 21 Aug 2023
Cited by 13 | Viewed by 3533
Abstract
The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation [...] Read more.
The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation and fibrosis which develop into cirrhosis. The human amniotic membrane (hAM), the innermost layer of the fetal placenta, is composed of multiple layers that include growth-factor rich basement membrane, epithelial and mesenchymal stromal cell layers. hAM possesses distinct beneficial anti-fibrotic, anti-inflammatory and pro-regenerative properties via the secretion of multiple potent trophic factors and/or direct differentiation into hepatic cells which place hAM-based therapies as potential therapeutic strategies for the treatment of chronic liver diseases. Decellularized hAM is also an ideal scaffold for liver tissue engineering as this biocompatible niche provides an excellent milieu for cell proliferation and hepatocytic differentiation. Therefore, the current review discusses the therapeutic potential of hAM and its derivatives in providing therapeutic solutions for liver pathologies including acute liver failure, metabolic disorders, liver fibrosis as well as its application in liver tissue engineering. Full article
(This article belongs to the Section Stem Cells)
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15 pages, 8652 KB  
Article
A Novel and Versatile Microfluidic Device for Cell Assays under Radio Frequency Exposure
by Mengshuang Wang, Mengni Zhu, Zhenjie Zhao, Xin Li and Jie Zhang
Biosensors 2023, 13(8), 763; https://doi.org/10.3390/bios13080763 - 27 Jul 2023
Viewed by 1755
Abstract
Wound healing is a complex process composed of different stages, which involves extensive communication between the different cellular factors of the extracellular matrix (ECM). The radio frequency electromagnetic field (RF-EMF) has been used to accelerate the wound-healing process and it has been found [...] Read more.
Wound healing is a complex process composed of different stages, which involves extensive communication between the different cellular factors of the extracellular matrix (ECM). The radio frequency electromagnetic field (RF-EMF) has been used to accelerate the wound-healing process and it has been found to enhance cell alignment and mobility. The conventional methods for cell mobility analysis in an electromagnetic field generated by a radiation source are not advisable due to the low-precision, nonuniform distribution of the field, low efficiency of the analysis in batch and the lack of system integration for autonomous on-body operation. Here, a novel and versatile electromagnetic exposure system integrated with a microfluidic chip was fabricated to explore the EMF-induced response. A gradient electromagnetic field in a two-dimensional plane has been successfully established in the microchambers placed along the field line. In this work, by deploying our radiation experiments in vitro, we validated the on-chip monitoring of cell response to exposure. This electromagnetic field was simulated and human amniotic epithelial cells (HAECs) were cultured in different microchambers for continuous exposure to the electromagnetic field excited by a monopole RF antenna (1.8 GHz). New protrusions were generated and an obvious increase in filopodia with the increased field intensity was investigated. Meanwhile, the variation in intracellular Ca2+ concentration under the electromagnetic field was examined. The inhibitory effect of the Ca2+ circulation was further inspected to reveal the potential downstream signaling pathway in the RF-EMF-related bioassay, suggesting that cytoskeletal dynamics of cells under exposure are highly associated with the EGF receptor (EGFR)-cytoskeleton downstream signaling pathway. Finally, the field-induced cell elongation and alignment parallel to the field direction were observed. Additionally, the subsequent recovery (field withdrawal) and re-establishment (field re-exposure) were explored. These results indicated that this reliable and versatile exposure system for bioassay could achieve precise and high-throughput detection of the RF-EMF-induced cytoskeletal reorganization in vitro and evaluate the possible health risk from RF-EMF exposure. Full article
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23 pages, 6424 KB  
Article
scRNA-Seq of Cultured Human Amniotic Fluid from Fetuses with Spina Bifida Reveals the Origin and Heterogeneity of the Cellular Content
by Athanasia Dasargyri, Daymé González Rodríguez, Hubert Rehrauer, Ernst Reichmann, Thomas Biedermann and Ueli Moehrlen
Cells 2023, 12(12), 1577; https://doi.org/10.3390/cells12121577 - 7 Jun 2023
Cited by 5 | Viewed by 3766
Abstract
Amniotic fluid has been proposed as an easily available source of cells for numerous applications in regenerative medicine and tissue engineering. The use of amniotic fluid cells in biomedical applications necessitates their unequivocal characterization; however, the exact cellular composition of amniotic fluid and [...] Read more.
Amniotic fluid has been proposed as an easily available source of cells for numerous applications in regenerative medicine and tissue engineering. The use of amniotic fluid cells in biomedical applications necessitates their unequivocal characterization; however, the exact cellular composition of amniotic fluid and the precise tissue origins of these cells remain largely unclear. Using cells cultured from the human amniotic fluid of fetuses with spina bifida aperta and of a healthy fetus, we performed single-cell RNA sequencing to characterize the tissue origin and marker expression of cultured amniotic fluid cells at the single-cell level. Our analysis revealed nine different cell types of stromal, epithelial and immune cell phenotypes, and from various fetal tissue origins, demonstrating the heterogeneity of the cultured amniotic fluid cell population at a single-cell resolution. It also identified cell types of neural origin in amniotic fluid from fetuses with spina bifida aperta. Our data provide a comprehensive list of markers for the characterization of the various progenitor and terminally differentiated cell types in cultured amniotic fluid. This study highlights the relevance of single-cell analysis approaches for the characterization of amniotic fluid cells in order to harness their full potential in biomedical research and clinical applications. Full article
(This article belongs to the Section Tissues and Organs)
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23 pages, 5568 KB  
Article
AEC and AFMSC Transplantation Preserves Fertility of Experimentally Induced Rat Varicocele by Expressing Differential Regenerative Mechanisms
by Alessia Peserico, Barbara Barboni, Valentina Russo, Delia Nardinocchi, Maura Turriani, Costanza Cimini, Nicola Bernabò, Ornella Parolini, Antonietta Rosa Silini, Ivana Antonucci, Liborio Stuppia, Paolo Berardinelli, Ilaria Falanga, Davide Perruzza, Luca Valbonetti and Annunziata Mauro
Int. J. Mol. Sci. 2023, 24(10), 8737; https://doi.org/10.3390/ijms24108737 - 14 May 2023
Cited by 3 | Viewed by 2643
Abstract
Amniotic membrane and amniotic fluid derived cells are regarded as a promising stem cell source for developing regenerative medicine techniques, although they have never been tested on male infertility diseases such as varicocele (VAR). The current study aimed to examine the effects of [...] Read more.
Amniotic membrane and amniotic fluid derived cells are regarded as a promising stem cell source for developing regenerative medicine techniques, although they have never been tested on male infertility diseases such as varicocele (VAR). The current study aimed to examine the effects of two distinct cell sources, human Amniotic Fluid Mesenchymal Stromal Cells (hAFMSCs) and amniotic epithelial cells (hAECs), on male fertility outcomes in a rat induced VAR model. To explain cell-dependent enhancement of reproductive outcomes in rats transplanted with hAECs and hAFMSCs, insights on testis morphology, endocannabinoid system (ECS) expression and inflammatory tissue response have been carried out alongside cell homing assessment. Both cell types survived 120 days post-transplantation by modulating the ECS main components, promoting proregenerative M2 macrophages (Mφ) recruitment and a favorable anti-inflammatory IL10 expression pattern. Of note, hAECs resulted to be more effective in restoring rat fertility rate by enhancing both structural and immunoresponse mechanisms. Moreover, immunofluorescence analysis revealed that hAECs contributed to CYP11A1 expression after transplantation, whereas hAFMSCs moved towards the expression of Sertoli cell marker, SOX9, confirming a different contribution into the mechanisms leading to testis homeostasis. These findings highlight, for the first time, a distinct role of amniotic membrane and amniotic fluid derived cells in male reproduction, thus proposing innovative targeted stem-based regenerative medicine protocols for remedying high-prevalence male infertility conditions such as VAR. Full article
(This article belongs to the Special Issue Stem Cells and Regenerative Medicine: In Vitro and In Vivo Studies)
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21 pages, 4079 KB  
Article
A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid
by Farhana Ferdousi, Kazunori Sasaki, Satoshi Fukumitsu, Hidetoshi Kuwata, Mitsutoshi Nakajima and Hiroko Isoda
Int. J. Mol. Sci. 2023, 24(9), 8077; https://doi.org/10.3390/ijms24098077 - 29 Apr 2023
Cited by 3 | Viewed by 2692
Abstract
Carnosic acid (CA) is a phenolic diterpene widely distributed in herbal plants, rosemary and sage. Although its medicinal properties, such as antioxidant, antimicrobial, and neuroprotective effects, have been well-documented, its relevant biochemical processes and molecular targets have not been fully explored yet. In [...] Read more.
Carnosic acid (CA) is a phenolic diterpene widely distributed in herbal plants, rosemary and sage. Although its medicinal properties, such as antioxidant, antimicrobial, and neuroprotective effects, have been well-documented, its relevant biochemical processes and molecular targets have not been fully explored yet. In the present study, we conducted an untargeted whole-genome transcriptomics analysis to investigate CA-induced early biological and molecular events in human amniotic epithelial stem cells (hAESCs) with the aim of exploring its multiple tissue-specific functionalities and potential molecular targets. We found that seven days of CA treatment in hAESCs could induce mesoderm-lineage-specific differentiation. Tissue enrichment analysis revealed that CA significantly enriched lateral plate mesoderm-originated cardiovascular and adipose tissues. Further tissue-specific PPI analysis and kinase and transcription factor enrichment analyses identified potential upstream regulators and molecular targets of CA in a tissue-specific manner. Gene ontology enrichment analyses revealed the metabolic, antioxidant, and antifibrotic activities of CA. Altogether, our comprehensive whole-genome transcriptomics analyses offer a thorough understanding of the possible underlying molecular mechanism of CA. Full article
(This article belongs to the Special Issue State-of-the-Art Bioactives and Nutraceuticals in Japan)
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15 pages, 2392 KB  
Article
Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma
by Hye-Rim Seong, Chan Ho Noh, Sangryong Park, Sumin Cho, Seok-Jin Hong, Ah-young Lee, Dongho Geum, Soon-Cheol Hong, Dongsun Park, Tae Myoung Kim, Ehn-Kyoung Choi and Yun-Bae Kim
Int. J. Mol. Sci. 2023, 24(9), 8073; https://doi.org/10.3390/ijms24098073 - 29 Apr 2023
Cited by 24 | Viewed by 3972
Abstract
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important [...] Read more.
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12–17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9–4.5 × 108 exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma. Full article
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13 pages, 2278 KB  
Article
Corneal Reconstruction with EGFP-Labelled Limbal Mesenchymal Stem Cells in a Rabbit Model of Limbal Stem Cell Deficiency
by Julia I. Khorolskaya, Daria A. Perepletchikova, Kirill E. Zhurenkov, Daniel V. Kachkin, Aleksandr A. Rubel, Miralda I. Blinova and Natalia A. Mikhailova
Int. J. Mol. Sci. 2023, 24(6), 5431; https://doi.org/10.3390/ijms24065431 - 12 Mar 2023
Cited by 5 | Viewed by 3285
Abstract
Ocular surface reconstruction is essential for treating corneal epithelial defects and vision recovery. Stem cell-based therapy demonstrates promising results but requires further research to elucidate stem cell survival, growth, and differentiation after transplantation in vivo. This study examined the corneal reconstruction promoted by [...] Read more.
Ocular surface reconstruction is essential for treating corneal epithelial defects and vision recovery. Stem cell-based therapy demonstrates promising results but requires further research to elucidate stem cell survival, growth, and differentiation after transplantation in vivo. This study examined the corneal reconstruction promoted by EGFP-labeled limbal mesenchymal stem cells (L-MSCs-EGFP) and their fate after transplantation. EGFP labeling allowed us to evaluate the migration and survival rates of the transferred cells. L-MSCs-EGFP seeded onto decellularized human amniotic membrane (dHAM) were transplanted into rabbits with a modeled limbal stem cell deficiency. The localization and viability of the transplanted cells in animal tissue were analyzed using histology, immunohistochemistry, and confocal microscopy up to 3 months after transplantation. EGFP-labeled cells remained viable for the first 14 days after transplantation. By the 90th day, epithelialization of the rabbit corneas reached 90%, but the presence of viable labeled cells was not observed within the newly formed epithelium. Although labeled cells demonstrated low survivability in host tissue, the squamous corneal-like epithelium was partially restored by the 30th day after transplantation of the tissue-engineered graft. Overall, this study paves the way for further optimization of transplantation conditions and studying the mechanisms of corneal tissue restoration. Full article
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18 pages, 3023 KB  
Article
A Novel Technique of Amniotic Membrane Preparation Mimicking Limbal Epithelial Crypts Enhances the Number of Progenitor Cells upon Expansion
by Jovana Bisevac, Morten Carstens Moe, Liv Drolsum, Olav Kristianslund, Goran Petrovski and Agate Noer
Cells 2023, 12(5), 738; https://doi.org/10.3390/cells12050738 - 24 Feb 2023
Cited by 5 | Viewed by 2132
Abstract
We aimed to investigate whether a novel technique of human amniotic membrane (HAM) preparation that mimics the crypts in the limbus enhances the number of progenitor cells cultured ex vivo. The HAMs were sutured on polyester membrane (1) standardly, to obtain a flat [...] Read more.
We aimed to investigate whether a novel technique of human amniotic membrane (HAM) preparation that mimics the crypts in the limbus enhances the number of progenitor cells cultured ex vivo. The HAMs were sutured on polyester membrane (1) standardly, to obtain a flat HAM surface, or (2) loosely, achieving the radial folding to mimic crypts in the limbus. Immunohistochemistry was used to demonstrate a higher number of cells positive for progenitor markers p63α (37.56 ± 3.34% vs. 62.53 ± 3.32%, p = 0.01) and SOX9 (35.53 ± 0.96% vs. 43.23 ± 2.32%, p = 0.04), proliferation marker Ki-67 (8.43 ± 0.38 % vs. 22.38 ± 1.95 %, p = 0.002) in the crypt-like HAMs vs. flat HAMs, while no difference was found for the quiescence marker CEBPD (22.99 ± 2.96% vs. 30.49 ± 3.33 %, p = 0.17). Most of the cells stained negative for the corneal epithelial differentiation marker KRT3/12, and some were positive for N-cadherin in the crypt-like structures, but there was no difference in staining for E-cadherin and CX43 in crypt-like HAMs vs. flat HAMs. This novel HAM preparation method enhanced the number of progenitor cells expanded in the crypt-like HAM compared to cultures on the conventional flat HAM. Full article
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