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Article ; Online: Human amniotic epithelial stem cells: Hepatic differentiation and regenerative properties in liver disease treatment.

Riedel, Rodrigo N / Pérez-Pérez, Antonio / Sánchez-Margalet, Víctor / Varone, Cecilia L / Maymó, Julieta L

2023 Volume 134, Page(s) 39–47

Abstract: The placenta and the extraembryonic tissues represent a valuable source of cells for regenerative medicine. In particular, the amniotic membrane possesses cells with stem cells characteristics that have attracted research attention. Human amniotic ... ...

Abstract	The placenta and the extraembryonic tissues represent a valuable source of cells for regenerative medicine. In particular, the amniotic membrane possesses cells with stem cells characteristics that have attracted research attention. Human amniotic epithelial cells (hAECs) have unique and desirable features that position them over other stem cells, not only because of the unlimited potential supplied of, the easy access to placental tissues, and the minimal ethical and legal barriers associated, but also due to the embryonic stem cells markers expression and their ability to differentiate into the three germ layers. In addition, they are non-tumorigenic and have immunomodulatory and anti-inflammatory properties. Hepatic failure is one of the major causes of morbidity and mortality worldwide. Organ transplantation is the best way to treat acute and chronic liver failure, but there are several associated obstacles. Stem cells have been highlighted as alternative hepatocytes source because of their potential for hepatogenic differentiation. HAECs, in particular, have some properties that make them suitable for hepatocyte differentiation. In this work, we review the general characteristics of the epithelial stem cells isolated from human amniotic membrane as well as their ability to differentiate to hepatic cells. We also revise their regenerative properties, with the focus on their potential application in the liver disease treatment.
MeSH term(s)	Humans ; Female ; Pregnancy ; Epithelial Cells ; Placenta ; Liver Diseases/therapy ; Cell Differentiation ; Embryonic Stem Cells
Language	English
Publishing date	2023-02-28
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	603951-0
ISSN	1532-3102 ; 0143-4004
ISSN (online)	1532-3102
ISSN	0143-4004
DOI	10.1016/j.placenta.2023.02.013
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Article ; Online: Myeloid-derived suppressor cells and vaccination against pathogens.

Prochetto, Estefanía / Borgna, Eliana / Jiménez-Cortegana, Carlos / Sánchez-Margalet, Víctor / Cabrera, Gabriel

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 1003781

Abstract: It is widely accepted that the immune system includes molecular and cellular components that play a role in regulating and suppressing the effector immune response in almost any process in which the immune system is involved. Myeloid-derived suppressor ... ...

Abstract	It is widely accepted that the immune system includes molecular and cellular components that play a role in regulating and suppressing the effector immune response in almost any process in which the immune system is involved. Myeloid-derived suppressor cells (MDSCs) are described as a heterogeneous population of myeloid origin, immature state, with a strong capacity to suppress T cells and other immune populations. Although the initial characterization of these cells was strongly associated with pathological conditions such as cancer and then with chronic and acute infections, extensive evidence supports that MDSCs are also involved in physiological/non-pathological settings, including pregnancy, neonatal period, aging, and vaccination. Vaccination is one of the greatest public health achievements and has reduced mortality and morbidity caused by many pathogens. The primary goal of prophylactic vaccination is to induce protection against a potential pathogen by mimicking, at least in a part, the events that take place during its natural interaction with the host. This strategy allows the immune system to prepare humoral and cellular effector components to cope with the real infection. This approach has been successful in developing vaccines against many pathogens. However, when the infectious agents can evade and subvert the host immune system, inducing cells with regulatory/suppressive capacity, the development of vaccines may not be straightforward. Notably, there is a long list of complex pathogens that can expand MDSCs, for which a vaccine is still not available. Moreover, vaccination against numerous bacteria, viruses, parasites, and fungi has also been shown to cause MDSC expansion. Increases are not due to a particular adjuvant or immunization route; indeed, numerous adjuvants and immunization routes have been reported to cause an accumulation of this immunosuppressive population. Most of the reports describe that, according to their suppressive nature, MDSCs may limit vaccine efficacy. Taking into account the accumulated evidence supporting the involvement of MDSCs in vaccination, this review aims to compile the studies that highlight the role of MDSCs during the assessment of vaccines against pathogens.
MeSH term(s)	Immunity ; Immunization ; Myeloid-Derived Suppressor Cells ; T-Lymphocytes ; Vaccination
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.1003781
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Article: Knowing the myeloid-derived suppressor cells: Another enemy of sarcomas patients.

García-Domínguez, Daniel J / Sánchez-Margalet, Víctor / de la Cruz-Merino, Luis / Hontecillas-Prieto, Lourdes

International review of cell and molecular biology

2023 Volume 375, Page(s) 93–116

Abstract: Sarcomas are heterogeneous and aggressive malignant tumors with variable responses to current standard treatments being usually incurable for those patients with metastatic and unresectable diseases. The lack of curative strategies has led to develop new ...

Abstract	Sarcomas are heterogeneous and aggressive malignant tumors with variable responses to current standard treatments being usually incurable for those patients with metastatic and unresectable diseases. The lack of curative strategies has led to develop new therapies in the treatment of sarcomas where the role of immune system is an evolving field. Most sarcomas often exhibit an immunosuppressive microenvironment, which reduces their capacity to trigger an immune response. Therefore, sarcomas are broadly considered as an "immune cold" tumor, although some studies have described a great immune heterogeneity across sarcoma subtypes. Sarcoma cells, like other tumors, evade their immune destruction through a variety of mechanisms, including expansion and recruitment of myeloid derived suppressor cells (MDSCs). MDSCs are immature myeloid cells that have been correlated with a reduction of the therapeutic efficacy, including immunotherapy, tumor progression and worst prognosis. Consequently, different strategies have been developed in recent years to target MDSCs in cancer treatments. This chapter discusses the role of MDSCs in sarcomas and their current potential as a therapeutic target in these malignancies.
MeSH term(s)	Humans ; Myeloid-Derived Suppressor Cells/pathology ; Neoplasms/pathology ; Sarcoma/therapy ; Sarcoma/pathology ; Immunotherapy ; Immune System/pathology ; Tumor Microenvironment
Language	English
Publishing date	2023-01-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2427220-6
ISSN	1937-6448 ; 0074-7696
ISSN	1937-6448 ; 0074-7696
DOI	10.1016/bs.ircmb.2022.11.003
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Article ; Online: Cancer Nano-Immunotherapy: The Novel and Promising Weapon to Fight Cancer.

García-Domínguez, Daniel J / López-Enríquez, Soledad / Alba, Gonzalo / Garnacho, Carmen / Jiménez-Cortegana, Carlos / Flores-Campos, Rocío / de la Cruz-Merino, Luis / Hajji, Nabil / Sánchez-Margalet, Víctor / Hontecillas-Prieto, Lourdes

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which ...

Abstract	Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano-immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.
MeSH term(s)	Humans ; Immunotherapy ; Neoplasms/therapy ; Antigen Presentation ; Immune Evasion ; Nanomedicine ; Tumor Microenvironment
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25021195
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Article ; Online: Dendritic cells: the yin and yang in disease progression.

Jiménez-Cortegana, Carlos / Palomares, Francisca / Alba, Gonzalo / Santa-María, Consuelo / de la Cruz-Merino, Luis / Sánchez-Margalet, Victor / López-Enríquez, Soledad

Frontiers in immunology

2024 Volume 14, Page(s) 1321051

Abstract: Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and ... ...

Abstract	Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the "yin-yang" role of DCs to improve the understand of this type of cells in disease progression.
MeSH term(s)	Humans ; Dendritic Cells ; Adaptive Immunity ; Neoplasms/metabolism ; Inflammatory Bowel Diseases ; Disease Progression
Language	English
Publishing date	2024-01-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1321051
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Article ; Online: Increasing the complexity of lipoprotein characterization for cardiovascular risk in type 2 diabetes.

Guardiola, Montse / Rehues, Pere / Amigó, Núria / Arrieta, Francisco / Botana, Manuel / Gimeno-Orna, José A / Girona, Josefa / Martínez-Montoro, José Ignacio / Ortega, Emilio / Pérez-Pérez, Antonio / Sánchez-Margalet, Víctor / Pedro-Botet, Juan / Ribalta, Josep

European journal of clinical investigation

2024 , Page(s) e14214

Abstract: The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent ... ...

Abstract	The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1-the information provided by routine clinical biochemistry, 2-advanced nuclear magnetic resonance (NMR)-based lipoprotein profiling and 3-the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein-related information into population-based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large-scale determination of these sets of methodologically diverse parameters.
Language	English
Publishing date	2024-04-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.14214
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Article ; Online: Possible Role of Leptin in Atopic Dermatitis: A Literature Review.

Jiménez-Cortegana, Carlos / Ortiz-García, Germán / Serrano, Amalia / Moreno-Ramírez, David / Sánchez-Margalet, Víctor

Biomolecules

2021 Volume 11, Issue 11

Abstract: Atopic dermatitis (AD) is the most frequent chronic inflammatory skin disease, and its incidence has been rapidly increasing in developed countries in the last years. AD presents a high degree of heterogeneity due to biases and confounding factors such ... ...

Abstract	Atopic dermatitis (AD) is the most frequent chronic inflammatory skin disease, and its incidence has been rapidly increasing in developed countries in the last years. AD presents a high degree of heterogeneity due to biases and confounding factors such as age range, sex, or ethnicity. For those reasons, the search for new biomarkers is crucial. At the same time, obesity, which is a global health problem, has also increased over the years. It has been associated with many pathophysiological states, including skin diseases such as AD, mostly in childhood. Obesity promotes a low grade inflammation driven by many different cytokines and adipokines, including leptin, which has a key role in many other diseases due to its pleiotropic effects. Leptin also has a role in both skin and allergic diseases very related to AD. Thus, this adipokine could have an important role in the pathogenesis of AD, especially in its chronicity. Despite the limited literature available, there is some evidence that leads us to consider leptin as an important adipokine in this skin disease. For this reason, here we have reviewed the role of leptin in the pathophysiology of AD.
MeSH term(s)	Cytokines ; Dermatitis, Atopic ; Leptin ; Skin
Chemical Substances	Cytokines ; Leptin
Language	English
Publishing date	2021-11-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11111642
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Article ; Online: Stem cells and COVID-19: are the human amniotic cells a new hope for therapies against the SARS-CoV-2 virus?

Riedel, Rodrigo N / Pérez-Pérez, Antonio / Sánchez-Margalet, Víctor / Varone, Cecilia L / Maymó, Julieta L

Stem cell research & therapy

2021 Volume 12, Issue 1, Page(s) 155

Abstract: A new coronavirus respiratory disease (COVID-19) caused by the SARS-CoV-2 virus, surprised the entire world, producing social, economic, and health problems. The COVID-19 triggers a lung infection with a multiple proinflammatory cytokine storm in severe ... ...

Abstract	A new coronavirus respiratory disease (COVID-19) caused by the SARS-CoV-2 virus, surprised the entire world, producing social, economic, and health problems. The COVID-19 triggers a lung infection with a multiple proinflammatory cytokine storm in severe patients. Without effective and safe treatments, COVID-19 has killed thousands of people, becoming a pandemic. Stem cells have been suggested as a therapy for lung-related diseases. In particular, mesenchymal stem cells (MSCs) have been successfully tested in some clinical trials in patients with COVID-19. The encouraging results positioned MSCs as a possible cell therapy for COVID-19. The amniotic membrane from the human placenta at term is a valuable stem cell source, including human amniotic epithelial cells (hAECs) and human mesenchymal stromal cells (hAMSCs). Interestingly, amnion cells have immunoregulatory, regenerative, and anti-inflammatory properties. Moreover, hAECs and hAMSCs have been used both in preclinical studies and in clinical trials against respiratory diseases. They have reduced the inflammatory response and restored the pulmonary tissue architecture in lung injury in vivo models. Here, we review the existing data about the stem cells use for COVID-19 treatment, including the ongoing clinical trials. We also consider the non-cellular therapies that are being applied. Finally, we discuss the human amniotic membrane cells use in patients who suffer from immune/inflammatory lung diseases and hypothesize their possible use as a successful treatment against COVID-19.
MeSH term(s)	Amnion/cytology ; COVID-19/therapy ; Clinical Trials as Topic ; Female ; Humans ; Inflammation ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Placenta/cytology ; Pregnancy ; Risk ; Stem Cells/cytology
Language	English
Publishing date	2021-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-021-02216-w
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Article ; Online: Decreased Expression of Sam68 Is Associated with Insulin Resistance in Granulosa Cells from PCOS Patients.

Vilariño-García, Teresa / Guadix, Pilar / Dorado-Silva, Mónica / Sánchez-Martín, Pascual / Pérez-Pérez, Antonio / Sánchez-Margalet, Víctor

Cells

2022 Volume 11, Issue 18

Abstract: Background and objective: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, obesity, and insulin resistance, which leads to subfertility. PCOS is the most frequent metabolic ... ...

Abstract	Background and objective: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, obesity, and insulin resistance, which leads to subfertility. PCOS is the most frequent metabolic disorder in women and the major cause of infertility. Susceptibility to developing PCOS is determined by a complex interaction between environmental and genetic factors. Although different mechanisms have been proposed to explain PCOS manifestations, defects in insulin actions or in the insulin signaling pathways are central in the pathogenesis of the syndrome. However, the mechanisms (molecular players and signaling pathways) underlying its primary origin still remain an unsolved issue. Current research is increasingly focusing on the discovery of novel biomarkers to further elucidate the complex pathophysiology of PCOS. Sam68, an RNA-binding protein, is recruited to insulin signaling, mediating different insulin actions. We aimed to investigate the role of Sam68 in insulin signaling and the possible implications of Sam68 in the insulin resistance in PCOS. Materials and methods: Granulosa cells were taken from women with PCOS (n = 25) and healthy donors (n = 25) and, within the age range of 20 to 42 years, from GINEMED, Assisted Reproduction Centre, Seville, Spain. The Sam68 expression level was analyzed both by qPCR and immunoblot. Statistical significance was assessed by one-way ANOVA, followed by a post-hoc test. A Results: We found that insulin stimulation increases the phosphorylation and expression level of Sam68 in granulosa cells from normal donors. The downregulation of Sam68 expression resulted in a lower activation of both the MAPK and the PI3K pathways in response to insulin. Moreover, the granulosa cells from the women with PCOS presented a lower expression of Sam68, as well as insulin receptor and insulin receptor substrate-1 (IRS-1). In these cells, the overexpression of Sam68 resulted in an increased activation of both the MAPK and the PI3K pathways in response to insulin. Conclusions: These results suggest the participation of Sam68 in insulin receptor signaling, mediating the insulin effect in granulosa cells, and they suggest the possible role of Sam68 in the insulin resistance of PCOS.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adult ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Female ; Granulosa Cells/metabolism ; Humans ; Insulin/metabolism ; Insulin Receptor Substrate Proteins/metabolism ; Insulin Resistance/physiology ; Phosphatidylinositol 3-Kinases/metabolism ; Polycystic Ovary Syndrome/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Receptor, Insulin/metabolism ; Young Adult
Chemical Substances	Adaptor Proteins, Signal Transducing ; DNA-Binding Proteins ; Insulin ; Insulin Receptor Substrate Proteins ; KHDRBS1 protein, human ; RNA-Binding Proteins ; Receptor, Insulin (EC 2.7.10.1)
Language	English
Publishing date	2022-09-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11182821
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Article ; Online: The effects of dendritic cell-based vaccines in the tumor microenvironment: Impact on myeloid-derived suppressor cells.

Sánchez-León, María Luisa / Jiménez-Cortegana, Carlos / Cabrera, Gabriel / Vermeulen, Elba Mónica / de la Cruz-Merino, Luis / Sánchez-Margalet, Victor

Frontiers in immunology

2022 Volume 13, Page(s) 1050484

Abstract: Dendritic cells (DCs) are a heterogenous population of professional antigen presenting cells whose main role is diminished in a variety of malignancies, including cancer, leading to ineffective immune responses. Those mechanisms are inhibited due to the ... ...

Abstract	Dendritic cells (DCs) are a heterogenous population of professional antigen presenting cells whose main role is diminished in a variety of malignancies, including cancer, leading to ineffective immune responses. Those mechanisms are inhibited due to the immunosuppressive conditions found in the tumor microenvironment (TME), where myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells known to play a key role in tumor immunoevasion by inhibiting T-cell responses, are extremely accumulated. In addition, it has been demonstrated that MDSCs not only suppress DC functions, but also their maturation and development within the myeloid linage. Considering that an increased number of DCs as well as the improvement in their functions boost antitumor immunity, DC-based vaccines were developed two decades ago, and promising results have been obtained throughout these years. Therefore, the remodeling of the TME promoted by DC vaccination has also been explored. Here, we aim to review the effectiveness of different DCs-based vaccines in murine models and cancer patients, either alone or synergistically combined with other treatments, being especially focused on their effect on the MDSC population.
MeSH term(s)	Humans ; Animals ; Mice ; Myeloid-Derived Suppressor Cells ; Tumor Microenvironment ; Neoplasms/therapy ; Myeloid Cells ; Dendritic Cells
Language	English
Publishing date	2022-11-15
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1050484
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