Current Tissue Engineering (Discontinued) - Volume 4, Issue 1, 2015

This review provides an overview of the Side Population (SP) phenotype related to stemness biology and tumorigenesis, highlighting the key technical mechanisms and biological processes involved. The actual challenges to fully exploit the possibilities provided by the SP phenotype in normal and cancer tissues are discussed. We put forward some suggestions for future research and the empowerment of a network of SP users to make the SP assay fully understood and technically scalable for its broader use.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells with unique biological properties, typically associated with their mesodermal lineage. Various in vitro studies and preclinical animal model showed that MSCs are promising for cell therapy showing the ability to home to sites of inflammation after tissue injury, to differentiate into various cell types and secrete multiple bioactive molecules capable of stimulating recovery of injured cells by inhibiting inflammation (known as paracrine effect). MSCs also show the lack of immunogenicity and have the ability to perform immunomodulatory functions. Undoubtedly the use of MSCs either taking advantage of their immunomodulatory properties or their ability to repair, with different cooperative mechanisms, an injured tissue will represent the standard therapy in the near future. However, there is a lack of consensus on several issues that need to be addressed: a better understanding of the MSCs mechanism of action, type of cells and sources, optimal cell dose and route of administration together with standardized Good Manufacturing Practice procedures and strict surveillance of genetic instability after multiple passages in culture. This concise review is not meant to be exhaustive on all diseases and conditions currently treated with MSCs, but only focuses on some pathologies (ischemic cardiovascular diseases, critical limb ischemia, bone and cartilage regeneration, neural diseases) at high socio-economic impact, that historically have been under investigation for regenerative purposes.

Background: Facial aging is a universal experience where an interplay of different tissue changes produces a progressive atrophy. Cosmetic medicine and surgery developed several useful physical and chemical techniques. Objective and Methods: The main purpose of this paper is a short review of the literature evaluating the application of stem cells in facial aging, their ability to get a multilineage differentiation and to introduce a safe and useful alternative way of harvesting and selection. Conclusion: The most common derivation of stem cells used in facial rejuvenation is from the adipose tissue. The possibility of selecting stromal stem cells directly from the lax subcutaneous connective tissue would allow a technical simplification in all the conditions in which the harvest of adipose tissue cannot be easily achieved, or where large amounts of injectable fat are not needed.

The skin, the largest organ of the body in vertebrates, represents approximately one-tenth of the body mass in humans. It is composed of the epidermis and dermis with a complex nerve and blood supply that provides vital barrier function. Disruption of epidermal integrity due to trauma, disease, burn or surgery can be fatal, and therefore strategies are needed to enhance the physiological regenerative properties of the skin. Tissue engineering, an evolving interdisciplinary field within biomedical engineering, aims for repair of diseased and damaged tissues, such as the skin. This requires a source of cells, but additionally, support from an artificial extracellular matrix (ECM), together with appropriate molecular signals. Engineered skin substitutes represent a developing source of advanced therapy in the clinical settings (e.g. use in acute and chronic skin wounds) as well as valuable skin surrogates for lab-based drug testing for permeability and toxicity. There has yet to be a model of bioengineered skin developed which replicates completely the appearance, structure, physiology and biological stability of uninjured skin. This paper discusses the use, advantages and disadvantages of skin equivalents and future directions of research in this field.

Background: Stem cell strategies and autologous bone grafting remain a gold standard for the reconstruction of bone defects in the maxillofacial region. In fact, maxillofacial tissue engineering aims to reconstruct and regenerate bone that simultaneously fulfills both morphological and functional restorations. For this purpose, scaffolds in combination with mesenchymal stem cells/osteoprogenitor cells and bioactive factors are necessary to recreate a 3D microenvironment that improves the quality of engineered tissues. Objective and Methods: The key objective of this mini-review is to analyze all the properties for the production of an engineered bone construct for maxillofacial tissue engineering, considering stem cells as a source and the different biomaterials used to support structures enhancing adhesion, proliferation and matrix production of seeded cells according to the circumstances of the bone defects. Results and Conclusion: In maxillofacial tissue engineering, dental pulp stem cells (DPSC) and bone-marrow mesenchymal stem cells (BMSC) represent the most common source of stem cells used for the fabrication of 3D structures, thanks to their ability of self-renewal and their capacity for multilineage differentiation. In addition, the identification of the most suitable scaffold allows soft-tissue regeneration and bone repair is strongly recommended for autologous micro-grafts. Fabrication of this 3D-culture will provide a powerful tool for regenerative medicine and may generate an adequate biocomplex to restore delicate maxillofacial and craniofacial anomalies.

Human tissue regeneration, especially the bone, today is one of the most important challenges for medicine and the need for this is particularly evident in the maxillo-facial area where it can be estimated that 1,500,000 patients in Europe undergo craniofacial reconstruction each year. Autologous bone is considered as the gold standard of bone graft materials, however, this approach is very limited. Recent research of non-embryonic stem cells provides new possibilities for no invasively obtaining new autologous bone from stem cells provided by various tissues from the same patient. Furthermore, in the literature, there are limited long-term data available mainly on the safe and efficacy of the prolonged use of stem cells. In this review, we will summarize the studies conducted on the regeneration, repair and rebuilding of craniofacial tissues using stem cells both in the presence or the absence of implantable biocompatible materials and the use of new micro-graft technologies, obtained through the Rigeneracons® medical device.

Cell therapy for the failing heart has advanced in distinct phases or era with a first transition from dynamic to cellular cardiomyoplasty. Currently, the quest is to find the optimal replacement cell type or to engineer a substitute for the dysfunctional scarred tissue. Cell therapies still require major refinements before they can—in a truly therapeutic manner—aid the suffering myocardium that fails either to adequately support contraction or to permit dilatation. Here, we outline the road so far and provide an insight into current and future challenges that await resolving.

Hyaluronic acid (HA) is a long-chain biopolymer that is used for a wide variety of therapeutic purposes because of its high biocompatibility and advantageous physico-chemical properties. Typical uses include surgical preparations, adhesion prevention, viscosupplementation and drug and cytokine delivery. Storage and release of desired factors can be effectively achieved when HA-based carriers are synthesized as hydrogels, although doing so normally requires chemical modification of the native HA structure. Delivery of stored solutes from these gels can be either “simple”, that is from a gel not including separate components intended to control release, or “regulated” when specific components are included for that purpose. A diverse assortment of modified forms of HA has been developed and used in therapeutic, clinical, veterinary and laboratory research environments, and the number of such applications is likely to grow in future years. In this article, we review recent developments in this field.

Therapeutic angiogenesis (TA) is a promising approach to improve impaired blood flow caused by ischemia. This approach is specifically applicable to patients with severe clinical limb ischemia (CLI) who have no alternatives to amputation. The TA contains three types of approaches: protein-based (i.e., using angiogenic factors), cell-based, and gene-based treatments. In this review, we describe the current state of protein-based TA to cure CLI and its future clinical application. Protein-based TA using angiogenic factors (e.g., fibroblast growth factor-2) combined with adequate carriers such as polymer-polysaccharide-based hydrogels for controlled-release may be the simple and convenient approach for current clinical applications, because of its less toxicity than gene-based method and less immunogenicity than cell-based method. The current accumulated preclinical and clinical data on TA will be helpful for preventing amputation in CLI patients and for treating various ischemic diseases. In addition, the data will provide valuable information for developing a technology towards regenerative medicine.