68 research outputs found
Obtaining Human Breast Adipose Cells for Breast Cancer Cell Co-culture Studies
Primary human breast cancers invade surrounding fat and contact adipocytes, inflammatory infiltrates, and fibrous stroma. This tissue niche influences breast tumor progression. Here, we present a protocol to enable the in vitro study of the complex interactions that occur between breast cancer cells and adipose cells. We describe how to obtain different adipose cell populations, including adipose-derived stem cells, immature adipocytes, and mature adipocytes, from human breast fat tissue and detail the application for co-culture assays with breast cancer cells. For complete details on the use and execution of this protocol, please refer to Picon-Ruiz et al. (2016) and Qureshi et al. (2020).This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 84510
Biofabrication of a tri-layered 3D-bioprinted CSC-based malignant melanoma model for personalized cancer treatment
Conventional in vitro cancer models do not accurately reproduce the tumor microenvironment
(TME), so three-dimensional (3D)-bioprinting represents an excellent tool to overcome their
limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by
cancer stem cells (CSCs) isolated from a MM established cell line or a primary-patient derived cell
line, fibroblasts, mesenchymal stem cells, and endothelial cells, embedded within an
agarose-collagen type I hydrogel were bioprinted. Embedded-cells showed high proliferation and
metabolic activity, and actively remodeled their TME. MM hydrogels displayed similar rheological
properties that skin and were able to support an early onset of vascularization. Besides, MM
hydrogels displayed different response to vemurafenib compared with cell cultures, and supported
tumorigenesis in murine xenotransplant achieving more mimetic in vivo models. For the first time
a tri-layered 3D-bioprinted CSC-based human MM model is developed recreating TME in vitro
and in vivo and response to treatment, being useful for precision treatment regimens against MM.Consejería
de Salud y Familias de la Junta de Andalucía (Project
No. PIN-0224-2019)Consejería de Economía,
Conocimiento, Empresas y Universidad de la Junta de
Andalucía (FEDER Funds, Projects PY18-FR-2470,
B-CTS-230-UGR18, A-CTS-180-UGR20, PYC20 RE
015 UGR and P18-FR-2465),Ministry de Economía
y Competitividad, Instituto de Salud Carlos
III (FEDER funds, Projects Nos. DTS19/00145
and DTS21/00098)Chair ‘Doctors
Galera-Requena in cancer stem cell research’ (CMCCTS963)Universidad
de Granada/CBUA.Plan Andaluz de Investigación,
Desarrollo e Innovación (PAIDI 2020—
FEDER funds—Ref: DOC_01574)
Dual Role of Fibroblasts Educated by Tumour in Cancer Behavior and Therapeutic Perspectives
Tumours are complex systems with dynamic interactions between tumour cells, nontumour
cells, and extracellular components that comprise the tumour microenvironment (TME). The
majority of TME’s cells are cancer-associated fibroblasts (CAFs), which are crucial in extracellular
matrix (ECM) construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour
cell motility. CAF subtypes have been identified based on the expression of protein markers. CAFs
may act as promoters or suppressors in tumour cells depending on a variety of factors, including
cancer stage. Indeed, CAFs have been shown to promote tumour growth, survival and spread, and
secretome changes, but they can also slow tumourigenesis at an early stage through mechanisms that
are still poorly understood. Stromal–cancer interactions are governed by a variety of soluble factors
that determine the outcome of the tumourigenic process. Cancer cells release factors that enhance the
ability of fibroblasts to secrete multiple tumour-promoting chemokines, acting on malignant cells
to promote proliferation, migration, and invasion. This crosstalk between CAFs and tumour cells
has given new prominence to the stromal cells, from being considered as mere physical support to
becoming key players in the tumour process. Here, we focus on the concept of cancer as a non-healing
wound and the relevance of chronic inflammation to tumour initiation. In addition, we review CAFs
heterogeneous origins and markers together with the potential therapeutic implications of CAFs
“re-education” and/or targeting tumour progression inhibition.Consejería de Economía, Conocimiento, Empresas y Universidad
de la Junta de Andalucía and European Regional Development Fund (ERDF), ref. P18-FR-2470,Ministry of Science, Innovation and Universities (ref. RTI2018-101309-B-C22)Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963
Clinical implications of inflammation in atheroma formation and novel therapies in cardiovascular diseases
PH-C is supported by an FPU grant from the Ministry of
Education, Culture and Sport. This work has been partially funded
by the University of Jaen, Acción I apoyo a la investigación (BIO-349)
and by Modeling Nature (MNat), Project number QUAL21-11.Cardiovascular diseases (CVD) are the leading causes of death and disability in the
world. Among all CVD, the most common is coronary artery disease (CAD). CAD
results from the complications promoted by atherosclerosis, which is
characterized by the accumulation of atherosclerotic plaques that limit and
block the blood flow of the arteries involved in heart oxygenation.
Atherosclerotic disease is usually treated by stents implantation and
angioplasty, but these surgical interventions also favour thrombosis and
restenosis which often lead to device failure. Hence, efficient and long-lasting
therapeutic options that are easily accessible to patients are in high demand.
Advanced technologies including nanotechnology or vascular tissue engineering
may provide promising solutions for CVD. Moreover, advances in the
understanding of the biological processes underlying atherosclerosis can lead
to a significant improvement in the management of CVD and even to the
development of novel efficient drugs. To note, over the last years, the
observation that inflammation leads to atherosclerosis has gained interest
providing a link between atheroma formation and oncogenesis. Here, we have
focused on the description of the available therapy for atherosclerosis, including
surgical treatment and experimental treatment, the mechanisms of atheroma
formation, and possible novel therapeutic candidates such as the use of anti-
inflammatory treatments to reduce CVD.FPU grant from the Ministry of Education, Culture and SportUniversity of Jaen, Accion I apoyo a la investigacion
BIO-349Modeling Nature (MNat)
QUAL21-1
Unifying Different Cancer Theories in a Unique TumourModel: Chronic Inflammation and Deaminases as Meeting Points
The increase in cancer incidences shows that there is a need to better understand tumour
heterogeneity to achieve efficient treatments. Interestingly, there are several common features among
almost all types of cancers, with chronic inflammation induction and deaminase dysfunctions singled
out. Deaminases are a family of enzymes with nucleotide-editing capacity, which are classified
into two main groups: DNA-based and RNA-based. Remarkably, a close relationship between
inflammation and the dysregulation of these molecules has been widely documented, which may
explain the characteristic intratumor heterogeneity, both at DNA and transcriptional levels. Indeed,
heterogeneity in cancer makes it difficult to establish a unique tumour progression model. Currently,
there are three main cancer models—stochastic, hierarchic, and dynamic—although there is no
consensus on which one better resembles cancer biology because they are usually overly simplified.
Here, to accurately explain tumour progression, we propose interactions among chronic inflammation,
deaminases dysregulation, intratumor genetic heterogeneity, cancer phenotypic plasticity, and even
the previously proposed appearance of cancer stem-like cell populations in the edges of advanced
solid tumour masses (instead of being the cells of origin of primary malignancies). The new tumour
development model proposed in this study does not contradict previously accepted models and it
may open up a window to interesting therapeutic approaches.FPU grant from the Ministry of Education, Culture and SportUniversity of Jaen, Accion I apoyo a la investigacion BIO-349Excellence Research Unit "Modeling Nature" (MNat)Junta de Andalucia
European Commission SOMM17/6109/UGRConsejeria de Salud y Familias de la Junta de Andalucia (FEDER funds) PEMP-0205-2020Ministry of Economy and Competitiveness (FEDER funds) PIE16/00045Ministry of Science, Innovation and Universities RTI2018-101309-B-C22Chair "Doctors Galera-Requena in cancer stem cell research" CMC-CTS96
Lipid-core nanoparticles: Classification, preparation methods, routes of administration and recent advances in cancer treatment
Nanotechnological drug delivery platforms represent a new paradigm for cancer therapeutics as they improve the
pharmacokinetic profile and distribution of chemotherapeutic agents over conventional formulations. Among
nanoparticles, lipid-based nanoplatforms possessing a lipid core, that is, lipid-core nanoparticles (LCNPs), have
gained increasing interest due to lipid properties such as high solubilizing potential, versatility, biocompatibility,
and biodegradability. However, due to the wide spectrum of morphologies and types of LCNPs, there is a lack of
consensus regarding their terminology and classification. According to the current state-of-the-art in this critical
review, LCNPs are defined and classified based on the state of their lipidic components in liquid lipid nanoparticles
(LLNs). These include lipid nanoemulsions (LNEs) and lipid nanocapsules (LNCs), solid lipid nanoparticles
(SLNs) and nanostructured lipid nanocarriers (NLCs). In addition, we present a comprehensive and
comparative description of the methods employed for their preparation, routes of administration and the
fundamental role of physicochemical properties of LCNPs for efficient antitumoral drug-delivery application.
Market available LCNPs, clinical trials and preclinical in vivo studies of promising LCNPs as potential treatments
for different cancer pathologies are summarized.MCIN/AEI FPU18/05336European Social Fund (ESF)Ph.D. program of Biomedicine of the University of GranadaMCIN/AEI/FEDER "Una manera de hacer Europa" RTI2018.101309B-C21
RTI2018.101309B-C2
Evolution of Metastasis Study Models toward MetastasisOn-A-Chip: The Ultimate Model?
For decades, several attempts have been made to obtain a mimetic model for
the study of metastasis, the reason of most of deaths caused by cancer, in
order to solve the unknown phenomena surrounding this disease. To better
understand this cellular dissemination process, more realistic models are
needed that are capable of faithfully recreating the entire and essential tumor
microenvironment (TME). Thus, new tools known as tumor-on-a-chip and
metastasis-on-a-chip have been recently proposed. These tools incorporate
microfluidic systems and small culture chambers where TME can be faithfully
modeled thanks to 3D bioprinting. In this work, a literature review has been
developed about the different phases of metastasis, the remaining unknowns
and the use of new models to study this disease. The aim is to provide a
global vision of the current panorama and the great potential that these
systems have for in vitro translational research on the molecular basis of the
pathology. In addition, these models will allow progress toward a personalized medicine, generating chips from patient samples that mimic the original
tumor and the metastatic process to perform a precise pharmacological
screening by establishing the most appropriate treatment protocol.Ministerio de Educacion y Formacion Profesional
FPU19/02138
BOE-B-2019-44783Ph.D. program of Biomedicine of the University of GranadaConsejeria de Economia, Conocimiento, Empresas y Universidad, Junta de Andalucia (FEDER Funds)
P18-FR-2470
B-CTS-230-UGR18
SOMM17/6109/UGRInstituto de Salud Carlos III (FEDER Funds)
PIE16-00045
DTS19/00145Junta de Andalucia
PIN-0224-2019Chair "Doctors Galera-Requena in cancer stem cell research"
CMC-CTS96
Eggshell Membrane as a Biomaterial for Bone Regeneration
The physicochemical features of the avian eggshell membrane play an essential role in
the process of calcium carbonate deposition during shell mineralization, giving rise to a porous
mineralized tissue with remarkable mechanical properties and biological functions. The membrane
could be useful by itself or as a bi-dimensional scaffold to build future bone-regenerative materials.
This review focuses on the biological, physical, and mechanical properties of the eggshell membrane
that could be useful for that purpose. Due to its low cost and wide availability as a waste byproduct of
the egg processing industry, repurposing the eggshell membrane for bone bio-material manufacturing
fulfills the principles of a circular economy. In addition, eggshell membrane particles have has the
potential to be used as bio-ink for 3D printing of tailored implantable scaffolds. Herein, a literature
review was conducted to ascertain the degree to which the properties of the eggshell membrane
satisfy the requirements for the development of bone scaffolds. In principle, it is biocompatible and
non-cytotoxic, and induces proliferation and differentiation of different cell types. Moreover, when
implanted in animal models, it elicits a mild inflammatory response and displays characteristics
of stability and biodegradability. Furthermore, the eggshell membrane possesses a mechanical
viscoelastic behavior comparable to other collagen-based systems. Overall, the biological, physical,
and mechanical features of the eggshell membrane, which can be further tuned and improved, make
this natural polymer suitable as a basic component for developing new bone graft materialsinisterio de Ciencia de Innovación (MCINN) (Ministry
of Science and Innovation, Spain) project PGC2018-102047-B-I00 (MCIU/AEI/FEDER/UE)Fundación
Mutua Madrileña, Grant/Award Number: FMM-AP17196-2019the Instituto de Salud Carlos
III, ERDF funds (DTS21/00098)the Consejería de Economía y Universidad, Junta de Andalucía
(PYC20 RE 015 UGR; P20_00208 of 2020)European Regional Development Fund (ERDF)–
Next Generation/EU program and grant AYUD/2022/33525 (FICYT)Canadian Natural Sciences and Engineering Research Council (NSERC, Discovery
program: RGPIN-2022-04803)PID2022-142886NB-I00 funded
by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe,” by the “European
Union.”The Ministerio de Ciencia Tecnología e Innovación (Ministry of Science, Technology, and
Innovation, Colombia) provided support for A.T-M´s participatio
Silver Nanoparticles from Annona muricata Peel and Leaf Extracts as a Potential Potent, Biocompatible and Low Cost Antitumor Tool
Cancer is one of the most prevalent diseases in the world and requires new therapies for
its treatment. In this context, the biosynthesis of silver nanoparticles (AgNPs) has been developed
to treat different types of tumors. The Annona muricata plant is known for having anticancer activity.
Its main compounds present in the leaves, stems and skin, allowing for its use as reducing agents.
In this manuscript, AgNPs with leaf extract (AgNPs-LE) and fruit peel extract (AgNPs-PE) of A.
muricata were biosynthesized obtaining an average nanoparticle diameter sizes smaller than 50 nm,
being 19.63 ± 3.7 nm and 16.56 ± 4.1 nm, and with a surface plasmonic resonance (SPR) at 447 and
448 nm, respectively. The lactone functional group present in the LE and PE extracts was identified
by the FTIR technique. The behavior and antiproliferation activity of AgNPs-LE and AgNPs-PE
were evaluated in breast, colon and melanoma cancer cell lines. Our results showed that Annona
muricata fruit peel, which is a waste product, has an antitumor effect more potent than leaf extract.
This difference is maintained with AgNPs where the destruction of cancer cells was, for the first
time, achieved using concentrations that do not exceed 3 μg/mL with a better therapeutic index in
the different tumor strains. In conclusion, we present a low-cost one-step experimental setup to
generate AgNPs-PE whose in-vitro biocompatibility and powerful therapeutic effect make it a very
attractive tool worth exploiting.Fundacion Empresa Universidad de Granada (Project
PR/18/001)Fundación Mutua Madrileña (Project FMM-AP16683-2017)Consejería de Salud Junta
de Andalucía (PI-0089-2017)Instituto de Salud Carlos III (RTI2018-101309-B-C22
Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use
Due to the great therapeutic interest that involves the translation of mesenchymal stromal cells (MSCs) into clinical practice, they have been widely studied as innovative drugs, in order to treat multiple pathologies. MSC-based cell therapy involves the administration of MSCs either locally or systemically into the receptor body where they can traffic and migrate towards the affected tissue and participate in the process of healing. The therapeutic effects of MSCs compromise of different mechanisms such as the functional integration of differentiated MSCs into diseased host tissue after transplantation, their paracrine support, and their impact on the regulation of both the innate and the acquired immune system. Here, we establish and provide recent advances about the principal mechanisms of action through which MSCs can perform their activity and effect as a therapeutic tool. The purpose of this review is to examine and discuss the MSCs capacity of migration, their paracrine effect, as well as MSC-mediated modifications on immune cell responses.This work was supported by the Fundación Mutua Madrileña (project FMM-AP17196-2019) and by the Ministerio de Economía, Industria y Competitividad (FEDER funds, project RTC-2016-5451-1)
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