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Article: Amnion-derived hydrogels as a versatile platform for regenerative therapy: from lab to market.

Kafili, Golara / Niknejad, Hassan / Tamjid, Elnaz / Simchi, Abdolreza

Frontiers in bioengineering and biotechnology

2024 Volume 12, Page(s) 1358977

Abstract: In recent years, the amnion (AM) has emerged as a versatile tool for stimulating tissue regeneration and has been of immense interest for clinical applications. AM is an abundant and cost-effective tissue source that does not face strict ethical issues ... ...

Abstract	In recent years, the amnion (AM) has emerged as a versatile tool for stimulating tissue regeneration and has been of immense interest for clinical applications. AM is an abundant and cost-effective tissue source that does not face strict ethical issues for biomedical applications. The outstanding biological attributes of AM, including side-dependent angiogenesis, low immunogenicity, anti-inflammatory, anti-fibrotic, and antibacterial properties facilitate its usage for tissue engineering and regenerative medicine. However, the clinical usage of thin AM sheets is accompanied by some limitations, such as handling without folding or tearing and the necessity for sutures to keep the material over the wound, which requires additional considerations. Therefore, processing the decellularized AM (dAM) tissue into a temperature-sensitive hydrogel has expanded its processability and applicability as an injectable hydrogel for minimally invasive therapies and a source of bioink for the fabrication of biomimetic tissue constructs by recapitulating desired biochemical cues or pre-defined architectural design. This article reviews the multi-functionality of dAM hydrogels for various biomedical applications, including skin repair, heart treatment, cartilage regeneration, endometrium regeneration, vascular graft, dental pulp regeneration, and cell culture/carrier platform. Not only recent and cutting-edge research is reviewed but also available commercial products are introduced and their main features and shortcomings are elaborated. Besides the great potential of AM-derived hydrogels for regenerative therapy, intensive interdisciplinary studies are still required to modify their mechanical and biological properties in order to broaden their therapeutic benefits and biomedical applications. Employing additive manufacturing techniques (e.g., bioprinting), nanotechnology approaches (e.g., inclusion of various bioactive nanoparticles), and biochemical alterations (e.g., modification of dAM matrix with photo-sensitive molecules) are of particular interest. This review article aims to discuss the current function of dAM hydrogels for the repair of target tissues and identifies innovative methods for broadening their potential applications for nanomedicine and healthcare.
Language	English
Publishing date	2024-02-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2024.1358977
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Article: Hypoxia-sensitive miRNA regulation

Yaghoobi, Alireza / Nazerian, Yasaman / Meymand, Arman Zeinaddini / Ansari, Ali / Nazerian, Amirhossein / Niknejad, Hassan

Frontiers in cell and developmental biology

2023 Volume 10, Page(s) 1082657

Abstract: Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of ... ...

Abstract	Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.1082657
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Article: Angiogenesis and Re-endothelialization in decellularized scaffolds: Recent advances and current challenges in tissue engineering.

Mazloomnejad, Radman / Babajani, Amirhesam / Kasravi, Mohammadreza / Ahmadi, Armin / Shariatzadeh, Siavash / Bahrami, Soheyl / Niknejad, Hassan

Frontiers in bioengineering and biotechnology

2023 Volume 11, Page(s) 1103727

Abstract: Decellularization of tissues and organs has recently become a promising approach in tissue engineering and regenerative medicine to circumvent the challenges of organ donation and complications of transplantations. However, one main obstacle to reaching ... ...

Abstract	Decellularization of tissues and organs has recently become a promising approach in tissue engineering and regenerative medicine to circumvent the challenges of organ donation and complications of transplantations. However, one main obstacle to reaching this goal is acellular vasculature angiogenesis and endothelialization. Achieving an intact and functional vascular structure as a vital pathway for supplying oxygen and nutrients remains the decisive challenge in the decellularization/re-endothelialization procedure. In order to better understand and overcome this issue, complete and appropriate knowledge of endothelialization and its determining variables is required. Decellularization methods and their effectiveness, biological and mechanical characteristics of acellular scaffolds, artificial and biological bioreactors, and their possible applications, extracellular matrix surface modification, and different types of utilized cells are factors affecting endothelialization consequences. This review focuses on the characteristics of endothelialization and how to optimize them, as well as discussing recent developments in the process of re-endothelialization.
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2023.1103727
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Article ; Online: Comparison of the effects of preservation methods on structural, biological, and mechanical properties of the human amniotic membrane for medical applications.

Jafari, Ameneh / Mirzaei, Yousef / Mer, Ali Hussein / Rezaei-Tavirani, Mostafa / Jafari, Zahra / Niknejad, Hassan

Cell and tissue banking

2023 Volume 25, Issue 1, Page(s) 305–323

Abstract: Amniotic membrane (AM), the innermost layer of the placenta, is an exceptionally effective biomaterial with divers applications in clinical medicine. It possesses various biological functions, including scar reduction, anti-inflammatory properties, ... ...

Abstract	Amniotic membrane (AM), the innermost layer of the placenta, is an exceptionally effective biomaterial with divers applications in clinical medicine. It possesses various biological functions, including scar reduction, anti-inflammatory properties, support for epithelialization, as well as anti-microbial, anti-fibrotic and angio-modulatory effects. Furthermore, its abundant availability, cost-effectiveness, and ethical acceptability make it a compelling biomaterial in the field of medicine. Given the potential unavailability of fresh tissue when needed, the preservation of AM is crucial to ensure a readily accessible and continuous supply for clinical use. However, preserving the properties of AM presents a significant challenge. Therefore, the establishment of standardized protocols for the collection and preservation of AM is vital to ensure optimal tissue quality and enhance patient safety. Various preservation methods, such as cryopreservation, lyophilization, and air-drying, have been employed over the years. However, identifying a preservation method that effectively safeguards AM properties remains an ongoing endeavor. This article aims to review and discuss different sterilization and preservation procedures for AM, as well as their impacts on its histological, physical, and biochemical characteristics.
MeSH term(s)	Pregnancy ; Female ; Humans ; Amnion/chemistry ; Cryopreservation/methods ; Freeze Drying/methods ; Placenta ; Biocompatible Materials/pharmacology
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2023-10-15
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2170897-6
ISSN	1573-6814 ; 1389-9333
ISSN (online)	1573-6814
ISSN	1389-9333
DOI	10.1007/s10561-023-10114-z
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Article: Effects of Different Perfusing Routes through The Portal Vein, Hepatic Vein, and Biliary Duct on Whole Rat Liver Decellularization.

Jambar Nooshin, Bahram / Tayebi, Tahereh / Babajani, Amirhesam / Khani, Mohammad Mehdi / Niknejad, Hassan

Cell journal

2023 Volume 25, Issue 1, Page(s) 35–44

Abstract: Objective: Organ transplantation is the last therapeutic choice for end-stage liver failure, which is limited by the lack of sufficient donors. Decellularized liver can be used as a suitable matrix for liver tissue engineering with clinical application ... ...

Abstract	Objective: Organ transplantation is the last therapeutic choice for end-stage liver failure, which is limited by the lack of sufficient donors. Decellularized liver can be used as a suitable matrix for liver tissue engineering with clinical application potential. Optimizing the decellularization procedure would obtain a biological matrix with completely removed cellular components and preserved 3-dimensional structure. This study aimed to evaluate the decellularization efficacy through three anatomical routes. Materials and methods: In this experimental study, rat liver decellularization was performed through biliary duct (BD), portal vein (PV), and hepatic vein (HV); using chemical detergents and enzymes. The decellularization efficacy was evaluated by measurement of DNA content, extracellular matrix (ECM) total proteins, and glycosaminoglycans (GAGs). ECM preservation was examined by histological and immunohistochemical (IHC) staining and scanning electron microscopy (SEM). Scaffold biocompatibility was tested by the MTT assay for HepG2 and HUVEC cell lines. Results: Decellularization through HV and PV resulted in a transparent scaffold by complete cell removal, while the BD route produced an opaque scaffold with incomplete decellularization. H and E staining confirmed these results. Maximum DNA loss was obtained using 1% and 0.5% sodium dodecyl sulfate (SDS) in the PV and HV groups and the DNA content decreased faster in the HV group. At the final stages, the proteins excreted in the HV and PV groups were significantly less than the BD group. The GAGs level was diminished after decellularization, especially in the PV and HV groups. In the HV and PV groups the collagen amount was significantly more than the BD group. The IHC and SEM images showed that the ECM structure was preserved and cellular components were entirely removed. MTT assay showed the biocompatibility of the decellularized scaffold. Conclusion: The results revealed that the HV is a more suitable route for liver decellularization than the PV and BD.
Language	English
Publishing date	2023-01-01
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2647430-X
ISSN	2228-5814 ; 2228-5806
ISSN (online)	2228-5814
ISSN	2228-5806
DOI	10.22074/cellj.2022.557600.1081
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Article ; Online: Tumor Targeting by Conditioned Medium Derived From Human Amniotic Membrane: New Insight in Breast Cancer Therapy.

Jafari, Ameneh / Rezaei-Tavirani, Mostafa / Niknejad, Hassan / Zali, Hakimeh

Technology in cancer research & treatment

2022 Volume 20, Page(s) 15330338211036318

Abstract: Objectives: Traditional breast cancer treatments have challenges including inefficiency, multidrug resistance, severe side effects, and targeting non-specifically. The development of alternative treatment strategies has attracted a great deal of ... ...

Abstract	Objectives: Traditional breast cancer treatments have challenges including inefficiency, multidrug resistance, severe side effects, and targeting non-specifically. The development of alternative treatment strategies has attracted a great deal of interest. Using the amniotic membrane has become a promising and convenient new approach for cancer therapy. This study aimed to evaluate the anti-cancer ability of conditioned medium extracted from the human amniotic membrane (hAM-CM) on breast cancer cells. Methods: Conditioned medium was collected after 48 h incubation of hAM in epithelial up manner. MTT, cell cycle, apoptosis, colony formation, and sphere assays were used to determine the impact of hAM-CM on breast cancer cell lines. The effects of hAM-CM on the migration and invasion of breast cancer cells were determined using scratch wound healing and transwell assays, respectively. Results: Based on the results, cell viability was significantly decreased by hAM-CM in a dose-dependent manner. The hAM-CM remarkably induced apoptosis and necrosis of cancer cells. Moreover, cell migration and invasion potential of cancer cells decreased after the hAM-CM treatment. Further, both the number of colonies and their morphologies were affected by the treatment. In the treated group, a significant decrease in the number of colonies along with an obvious change in their morphologies from holoclone shape to a dominant paracolone structure was observed. Conclusion: Our results indicate that the conditioned medium derived from the human amniotic membrane able to inhibit proliferation and metastasis of tumor cells and can be considered a natural and valuable candidate for breast cancer therapy.
MeSH term(s)	Amnion/cytology ; Apoptosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cell Cycle Checkpoints ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Female ; Humans
Chemical Substances	Culture Media, Conditioned
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2146365-7
ISSN	1533-0338 ; 1533-0346
ISSN (online)	1533-0338
ISSN	1533-0346
DOI	10.1177/15330338211036318
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Zs.A 5871: Show issues

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Article: The Synergistic Anti-Apoptosis Effects of Amniotic Epithelial Stem Cell Conditioned Medium and Ponesimod on the Oligodendrocyte Cells.

Safaeinejad, Fahimeh / Asadi, Sareh / Ghafghazi, Shiva / Niknejad, Hassan

Frontiers in pharmacology

2021 Volume 12, Page(s) 691099

Abstract: Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and ... ...

Abstract	Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and eventually neurons. So, we need new approaches for axonal protection and remyelination. Amniotic epithelial stem cells amniotic epithelial cells, as a neuroprotective and neurogenic agent, are a proper source in tissue engineering and regenerative medicine. Due to differentiation capability and secretion of growth factors, AECs can be a candidate for the treatment of MS. Moreover, sphingosine-1-phosphate (S1P) receptor modulators were recently approved by FDA for MS. Ponesimod is an S1P receptor-1 modulator that acts selectively as an anti-inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. In this study, due to the characteristics of AECs, they are considered a treatment option in MS. The conditioned medium of AECs concurrently with ponesimod was used to evaluate the viability of the oligodendrocyte cell line after induction of cell death by cuprizone. Cell viability after treatment by conditioned medium and ponesimod was increased compared to untreated groups. Also, the results showed that combination therapy with CM and ponesimod had a synergistic anti-apoptotic effect on oligodendrocyte cells. The combination treatment with CM and ponesimod reduced the expression of caspase-3, caspase-8, Bax, and Annexin V proteins and increased the relative BCL-2/Bax ratio, indicating inhibition of apoptosis as a possible mechanism of action. Based on these promising results, combination therapy with amniotic stem cells and ponesimode could be a proper alternative for multiple sclerosis treatment.
Language	English
Publishing date	2021-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.691099
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Article: Developing Cytokine Storm-Sensitive Therapeutic Strategy in COVID-19 Using 8P9R Chimeric Peptide and Soluble ACE2.

Nazerian, Yasaman / Vakili, Kimia / Ebrahimi, Ali / Niknejad, Hassan

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 717587

Abstract: Currently, the COVID-19 pandemic is an international challenge, largely due to lack of effective therapies. Pharmacotherapy has not yet been able to find a definitive treatment for COVID-19. Since SARS-CoV-2 affects several organs, treatment strategies ... ...

Abstract	Currently, the COVID-19 pandemic is an international challenge, largely due to lack of effective therapies. Pharmacotherapy has not yet been able to find a definitive treatment for COVID-19. Since SARS-CoV-2 affects several organs, treatment strategies that target the virus in a wider range are expected to be ultimately more successful. To this end, a two-step treatment strategy has been presented. In the first phase of the disease, when the patient is newly infected with the virus and the cytokine storm has not yet been developed, a chimeric peptide is used to inhibit virus entry into the host cell cytosol (by inhibiting endosomal pH acidification) and viral replication. After the virus entry and decrease of angiotensin converting enzyme 2 (ACE2) level, some people are unable to properly compensate for the ACE2 pathway and progress toward the cytokine storm. In the beginning of the cytokine storm, sACE2 protein is very effective in regulating the immune system toward the anti-inflammatory pathway, including M2 macrophages. Hence, the genes of 8P9R chimeric peptide and sACE2 would be inserted in an episomal vector with a separate promoter for each gene: the chimeric peptide gene promoter is a CMV promoter, while the sACE2 gene promoter is a NF-κB-sensitive promoter. The NF-κB-sensitive promoter induces the expression of sACE2 gene soon after elevation of NF-κB which is the main transcription factor of inflammatory genes. Thus, as the expression of inflammatory cytokines increases, the expression of sACE2 increases simultaneously. In this condition, sACE2 can prevent the cytokine storm by inhibiting the pro-inflammatory pathways. To deliver the designed vector to the target cells, mesenchymal stem cell-derived (MSC-derived) exosome-liposome hybrids are used. Herein, the strategy can be considered as a personalized clinical therapy for COVID-19, that can prevent morbidity and mortality in the future.
Language	English
Publishing date	2021-09-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.717587
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Article ; Online: Proposed Mechanisms of Targeting COVID-19 by Delivering Mesenchymal Stem Cells and Their Exosomes to Damaged Organs.

Jamshidi, Elham / Babajani, Amirhesam / Soltani, Pegah / Niknejad, Hassan

Stem cell reviews and reports

2021 Volume 17, Issue 1, Page(s) 176–192

Abstract: With the outbreak of coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world has been facing an unprecedented challenge. Considering the lack of appropriate therapy for COVID-19, it is ... ...

Abstract	With the outbreak of coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world has been facing an unprecedented challenge. Considering the lack of appropriate therapy for COVID-19, it is crucial to develop effective treatments instead of supportive approaches. Mesenchymal stem cells (MSCs) as multipotent stromal cells have been shown to possess treating potency through inhibiting or modulating the pathological events in COVID-19. MSCs and their exosomes participate in immunomodulation by controlling cell-mediated immunity and cytokine release. Furthermore, they repair the renin-angiotensin-aldosterone system (RAAS) malfunction, increase alveolar fluid clearance, and reduce the chance of hypercoagulation. Besides the lung, which is the primary target of SARS-CoV-2, the heart, kidney, nervous system, and gastrointestinal tract are also affected by COVID-19. Thus, the efficacy of targeting these organs via different delivery routes of MSCs and their exosomes should be evaluated to ensure safe and effective MSCs administration in COVID-19. This review focuses on the proposed therapeutic mechanisms and delivery routes of MSCs and their exosomes to the damaged organs. It also discusses the possible application of primed and genetically modified MSCs as a promising drug delivery system in COVID-19. Moreover, the recent advances in the clinical trials of MSCs and MSCs-derived exosomes as one of the promising therapeutic approaches in COVID-19 have been reviewed.
MeSH term(s)	COVID-19/immunology ; COVID-19/therapy ; COVID-19/virology ; Exosomes/immunology ; Humans ; Immunomodulation/immunology ; Lung/immunology ; Lung/pathology ; Lung/virology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/immunology ; SARS-CoV-2/pathogenicity
Language	English
Publishing date	2021-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-020-10109-3
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Zs.A 6198: Show issues

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Article: ERRATUM: The biological mechanism involved in anticancer properties of amniotic membrane.

Jafari, Ameneh / Niknejad, Hassan / Rezaei-Tavirani, Mostafa / Zali, Hakimeh

Oncology reviews

2021 Volume 15, Issue 1, Page(s) 536

Language	English
Publishing date	2021-03-05
Publishing country	Italy
Document type	Journal Article ; Published Erratum
ZDB-ID	2390302-8
ISSN	1970-5565 ; 1970-5565 ; 1970-5557
ISSN (online)	1970-5565
ISSN	1970-5565 ; 1970-5557
DOI	10.4081/oncol.2021.536
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