Gema Jiménez González

• PhD
• PhD at University of Granada

To overcome the limitations of conventional skin tissue engineering (TE), 3D biofabrication approaches are being developed. However, tissue mimicry should be further improved in skin models. Here, we developed and characterized biomimetic hydrogels to obtain a biofabricated three-layered (BT) skin substitute based on the main components found in th...

Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that clos...

There is increasing evidence that cancer progression is linked to tissue viscoelasticity, which challenges the commonly accepted notion that stiffness is the main mechanical hallmark of cancer. However, this new insight has not reached widespread clinical use, as most clinical trials focus on the application of tissue elasticity and stiffness in di...

Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, i...

Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and hig...

Conventional in vitro cancer models do not accurately reproduce the tumor microenvironment, so 3D-bioprinting represents an excellent tool to overcome their limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by cancer stem cells isolated from a MM established cell line or a primary-patient derived cell line, fi...

Bioprinting In article 2200251 by Gema Jiménez, Juan Antonio Marchal and co‐workers, a tissue graft made by a b‐TPUe scaffold is modified with two methods based on 1‐pyrene butyric acid (PBA) and Collagen type I. The two methods enhance the mesenchymal stem cell–biomaterial interactions and the improvement in chondro‐inductive properties, which has...

Osteoarthritis is a disease with a great socioeconomic impact and mainly affects articular cartilage, a tissue with reduced self‐healing capacity. In this work, 3D printed 1,4 butanediol thermoplastic polyurethane (b‐TPUe) scaffolds are functionalized and infrapatellar mesenchymal stem cells are used as the cellular source. Since b‐TPUe is a biomat...

The complexity of the tumor microenvironment (TME) together with the development of the metastatic process are the main reasons for the failure of conventional anticancer treatment. In recent years, there is an increasing need to advance towards advanced in vitro models of cancer mimicking TME and simulating metastasis in order to understand the as...

Brief Commentary Background: A deeper knowledge of the functional versatility and dynamic nature of the ECM has improved the understanding of cancer biology. Translational Significance: This work provides an in-depth view of the importance of the ECM to develop more mimetic breast cancer models, which aim to recreate the components and architecture...

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...

The use of decellularized extracellular matrix (dECM) as a biomaterial has been an important step forward for the development of functional tissue constructs. In addition to tissues and organs, cell cultures are gaining a lot of attention as an alternative source of dECM. In this work, a novel biomimetic hydrogel is developed based on dECM obtained...

The most pressing need in cartilage tissue engineering (CTE) is the creation of a biomaterial capable to tailor the complex extracellular matrix of the tissue. Despite the standardized used of polycaprolactone (PCL) for osteochondral scaffolds, the pronounced stiffness mismatch between PCL scaffold and the tissue it replaces remarks the biomechanic...

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a...

Tissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage‐like mechanical properties capable of sustaining high load‐bearing environments to integrate into the surrounding tissue of the...

In the present study, semi- and interpenetrated polymer network (IPN) systems based on hyaluronic acid (HA) and chitosan using ionic crosslinking of chitosan with a bioactive crosslinker, glycerylphytate (G1Phy), and UV irradiation of methacrylate were developed, characterized and evaluated as potential supports for tissue engineering. Semi- and IP...

The importance of the microenvironment in tumor development and their resistance to drugs is increasingly well known. This microenvironment is composed of different cell types, among which cells with stemness properties such as cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) are distinguished for their relevant role in tumor proliferatio...

Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironm...

The use of nanotechnology has become a promising approach in the treatment of cancer. However, most intravenously injected nanoparticles (NPs) do not effectively reach the tumor mass due to the biological barriers in the body. In an attempt to unify clinical criteria and basic research, we have collected the latest studies and described novel alter...

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on ce...

In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we...

Bioprinting is a promising tool to fabricate well-organized cell-laden constructs for repair and regeneration of articular cartilage. The selection of a suitable bioink, in terms of composition and mechanical properties, is crucial for the development of viable cartilage substitutes. In this study, we focused on the use of one of the main cartilage...

Colorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their u...

Due to the high prevalence of cancer in recent years, it is necessary to develop new and more effective therapies that produce fewer side effects. Development of gene therapy for cancer based on the use of suicide genes that can damage the tumor cell, without requiring a prodrug for its lethal effect, is one of the recent foci of gene therapy strat...

Cartilage degeneration or damage treatment is still a challenge, but, tissue engineering strategies, which combine cell therapy strategies, which combine cell therapy and scaffolds, and have emerged as a promising new approach. In this regard, polyurethanes and polyacrylates polymers have been shown to have clinical potential to treat osteochondral...

Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks, and the hazards of thrombus formation still need to be addressed. In this study, we assess the mechanical properties of two groups of po...

yaluronic acid (HA), as one of the main components of the extracellular matrix (ECM), plays a significant role in a multitude of biological processes involving cell migration, proliferation, differentiation, wound healing and inflammation. Thanks to its excellent biocompatibility, biodegradability and hygroscopic properties, HA has been used in its...

Osteoarthritis (OA) is a joint disorder that is highly extended in the global population. Several researches and therapeutic strategies have been probed on OA but without satisfactory long-term results in joint replacement. Recent evidences show how the cartilage biomechanics plays a crucial role in tissue development. This review describes how phy...

Despite the great advances in cancer treatment, colorectal cancer has emerged as the second highest cause of death from cancer worldwide. For this type of tumor, the use of suicide gene therapy could represent a novel therapy. We recently demonstrated that co-expression of gef and apoptin dramatically inhibits proliferation of the DLD-1 colon cell...

Impact statement: 3D bioprinting represents a novel advance in the area of regenerative biomedicine and tissue engineering for the treatment of different pathologies, among which are those related to cartilage. Currently, the use of different thermoplastic polymers, such as PLA or PCL, for bioprinting processes presents an important limitation: th...

Engineered cartilage tissue is one of the most promising treatments for articular cartilage pathologies. In this work, an ultrasonic bioreactor was designed to implement a non-invasive real-time monitoring of the neo-cartilage tissue formation processes through signal analysis. Polylactic acid (PLA) scaffolds were printed and seeded with human chon...

The lack of an effective treatment against cancer is not only due to its huge heterogeneity, but also to the fact that we don't have an answer to the question on how cancer originates. Among the proposed models to explain the development of cancer, the hierarchical model has been widely accepted. Nevertheless, this model fails to explain several ex...

Purpose: Based on the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed in triple negative breast cancer (TNBC) patients, but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to...

New treatment modalities are urgently needed to better manage advanced breast cancer. Combination therapies are usually more effective than monotherapy. In this context, the use of cyclic and acyclic O,N-acetals derivative compounds in combination with the suicide gef gene shown a potent anti-tumour activity and represent a new generation of antica...

Osteoarthritis (OA) is the most prevalent joint disease characterized by pain and degenerative lesions of the cartilage, subchondral bone, and other joint tissues. The causes of OA remain incompletely understood. Over the years, it has become recognized that OA is a multifactorial disease. In particular, aging and trauma are the main risk factors i...

Osteochondral (OC) lesions are a major cause of chronic musculoskeletal pain and functional disability, which reduces the quality of life of the patients and entails high costs to the society. Currently, there are no effective treatments, so in vitro and in vivo disease models are critically important to obtain knowledge about the causes and to dev...

Cancer stem cells (CSCs) are responsible for tumour initiation, metastasis and cancer recurrence, however the involvement of microenvironment is crucial. Here, we have analyzed how human mesenchymal stem cells (MSCs)-derived conditioned medium (CM) affect colon and melanoma CSCs enrichment and maintenance. Our results strongly suggest that the secr...

The success of cell-based approaches for the treatment of cartilage defects requires an optimal autologous cell source with chondrogenic differentiation ability that maintains its differentiated properties and stability following implantation. The objective of this study was to compare the chondrogenic capacity of mesenchymal stem cells (MSCs) isol...

Engineered cartilage tissue is one of the most promising treatments for articular cartilage defects. In this study, a bioreactor was designed to implement a non-invasive real-time monitoring of the neo-cartilage tissue formation processes through ultrasonic signal analysis. Polylactic acid (PLA) scaffolds were printed and seeded with human chondroc...

I Jornada de Neurocientíficas, Instituto de Neurociencias de la Universidad de Granada. Granada, España. 12/02/2018.

The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attentio...

The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, th...

I Jornadas Científicas del Centro de Investigación Biomédica, Universidad de Granada. Granada, España. 21/06/2017.

Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine...

Introducción Los avances en bioimpresión de tejidos y órganos (bioprinting), han generando en los últimos años una nueva alternativa tecnológica capaz de fabricar piezas malladas tridimensionales combinadas con células que posibilitan la generación de tejidos in vitro con aplicación en el campo de la ingeniería tisular y medicina regenerativa. El c...

Introduction: Despite clinical efforts, treatments to heal osteochondral lesions remain inefficient and frequently result, long-term, in joint arthroplasty. The complex structure of cartilage tissue, composed of a highly hydrated extracellular matrix (ECM), an avascular nature, and slow cellular turnover, hamper tissue regeneration after trauma or...

Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon canc...

Classically, two types of adipose tissue have been described: the white adipose tissue (WAT) and the brown adipose tissue (BAT), mainly composed by white and brown adipocytes, respectively. These adipocytes present different characteristics, while white adipocytes plays a role in energy storage by containing lipids in a single large lipid droplet,...

A bioreactor has been designed to achieve a real-time testing of a tissue by means of ultrasonic signal analysis. Polylactic acid (PLA) bioprinted scaffolds were seeded with human chondrocytes. Then, scaffolds were introduced into the bioreactor and cells were monitored by an ultrasonic sine-burst of 1 MHz during 4 weeks. From a mechanical standpoi...

Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patien...

XVI European Society of Sports Traumatology, Knee Surgery and Arthroscopy. Amsterdam, Holanda. 14-17/05/2014. doi: 10.1007/s00167-014-2917-5

Identification of novel anticancer drugs presenting more than one molecular target and efficacy against cancer stem-like cells (CSCs) subpopulations represents a therapeutic need to combat the resistance and the high risk of relapse in patients. In the present work we show how Bozepinib [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetra...

I Jornada Doctoral de la Universidad de Jaén. Jaén, España. 29/11/2013.

Bozepinib [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine] is a potent antitumor compound that is able to induce apoptosis in breast cancer cells. In the present study, we show that bozepinib also has antitumor activity in colon cancer cells, showing 50% inhibitory concentration (IC50) values low...

Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell ther...

In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissu...

Objective: Infrapatellar fat pad of patients with osteoarthritis (OA) contains multipotent and highly clonogenic adipose-derived stem cells that can be isolated by low invasive methods. Moreover, nuclear and cytoplasmic cellular extracts have been showed to be effective in induction of cell differentiation and reprogramming. The aim of this study...

This book looks at the latest research studies on apoptosis in medicine. It is divided into three sections for convenient and easy reading. The first section which comprises two chapters is an introduction of the subject of apoptosis to the uninitiated. The second section which comprises a single solitary chapter looks at apoptosis in normal physio...