Elena López-Ruiz

Functionalized Nanostructures with Application in Regenerative Medicine

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 tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.

How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

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 therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac.

Polymers, scaffolds and bioactive molecules with therapeutic properties in osteochondral pathologies: what’s new?

ABSTRACT 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 disease. Tissue engineering provides new promising alternatives to current treatments designed to regenerate osteochondral defects. Area covered: This review describes current and recent strategies of enhancing osteochondral repair through the use of cells, scaffolds, and bioactive molecules. Here, we review the latest (2011–2015) innovative patents in osteochondral regeneration, emphasizing novel strategies for articular cartilage repair. Finally, we present a summary of ongoing clinical trials that are testing innovative engineered products. Expert opinion: Promising tissue engineering based procedures have emerged as a therapeutic option for the treatment of osteochondral lesions. The development of multilayer scaffolds and the controlled release of bioactive molecules to promote in situ regeneration of both cartilage and bone are some of the latest technologies that intended to improve on the available traditional treatments. To confirm the potential of these novel approaches, long-term evaluation is necessary with special focus on studying the biological and mechanical proprieties of the synthesized tissues.

Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile

Cancer stem cells (CSCs) are responsible for tumor 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 secretome of CM-MSCs selects and maintains subpopulations with high expression of CSCs markers and ALDH1 activity, low proliferation rates with G1 phase arrest, and notably retain in vivo these properties. Cytogenetic analyses indicated that CM-cultured cells contain alterations in chromosome 17 (17q25). Subsequent SKY-FISH analyses suggested that genes located in 17q25 might be involved in stem-cell maintenance. The characterization of secreted proteins present in CM-MSCs revealed that four cytokines and seven growth factors are directly linked to the CSCs enrichment reported in this study. Further analyses revealed that the combination of just IL6 and HGF is enough to provide cancer cells with better stemness properties. In conclusion, this study demonstrates how specific chromosomal alterations present in CSCs subpopulations might represent an advantage for their in vitro maintenance and in vivo stemness properties.

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

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 carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels.

Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives

© 2012 Marchal et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives

Models of Disease

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 develop effective treatments for OC injuries. In vitro models are essential to clarify the causes of the disease and the subsequent design of the first barrier to test potential therapeutics. On the other hand, in vivo models are anatomically more similar to humans allowing to reproduce the pattern and progression of the lesion in a controlled scene and offering the opportunity to study the symptoms and responses to new treatments. Moreover, in vivo models are the most suitable preclinical model, being a fundamental and a mandatory step to ensure the successful transfer to clinical trials. Both in vitro and in vitro models have a number of advantages and limitation, and the choice of the most appropriate model for each study depends on many factors, such as the purpose of the study, handling or the ease to obtain, and cost, among others. In this chapter, we present the main in vitro and in vivo OC disease models that have been used over the years in the study of origin, progress, and treatment approaches of OC defects.

A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer

Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP’s anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

Brown Adipose Tissue and Obesity

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, brown adipocytes activate adaptive thermogenesis controlling energy expenditure. In addition, recently the so called “brite” or “beige” adipose tissue has been found within certain WAT depots, and appear functionally similar to classical brown adipocytes. In this chapter we describe the main characteristics of BAT, by highlighting that makes it unique and different from WAT, including its localization in humans, origin and differentiation, physiology and molecular regulation. Moreover, we show its role in obesity and associated pathologies and how we can harness the anti-obesity potential for future therapeutic strategies.