Frontiers in Stem Cell and Regenerative Medicine Research

The classical cancer stem cell theory (CCSCT) proposes that tumors contain a subpopulation of rare cancer cells with stem-like properties (cancer stem cells, CSCs) that are organized hierarchically and are responsible for chemoresistance and tumor relapse. In this model, CSCs can generate non-CSCs, but this process is irreversible (unidirectional model). Experimental data provided evidence that cancer cells are extremely plastic in terms of stemness and that both CSCs and non-CSCs can interconvert into each other. As a result, alternative models of cancer stem cell biology such as the Stemness Phenotype Model, the Complex System Model, the Dynamic CSC Model and the Reprogramming Model have been proposed to reconcile experimental data with the working models of CSCs. These alternative models have profound implications for the development of new therapeutic strategies for cancer treatment. The aim of this chapter is to provide an overview of each of these alternative models of CSCs, their clinical implications and to discuss potential strategies to develop more effective therapeutic regimens for cancer treatment.

Mesenchymal stromal/stem cells (MSCs) represent suitable candidates for regenerative medicine purposes given their ability to differentiate in several cellular lineages, to migrate to site of injury, to secrete soluble factors crucial for cell survival and proliferation, as well as to modulate immune response. Although the exact mechanisms of action are still under investigation, several MSC- based clinical trials developed for various diseases, including organ injuries, systemic diseases, chronic inflammatory and autoimmune pathologies are ongoing. Recently, the possibility of using less immunogenic and more specific MSC by-products (i.e. microvesicles and exosomes) to overcome MSC transplantation criticisms and side effects is currently under consideration.

Scientific and technical advancements in the field of orthopaedic surgery have allowed for improved patient outcomes and fewer complications; however, many orthopaedic conditions still have no curative treatment options. The use of stem cells has gained significant scientific interest to treat common orthopaedic conditions due to their innate properties. Stem cells are proliferative, pluripotent, mobile, and able to exert paracrine effects when stimulated, stimulating the healing process. Mesenchymal stem cells have garnered the most attention in orthopaedics due to their connective tissue lineage, which allows them to differentiate into chondrocytes, tenocytes, and osteoblasts. Allogenic, amniotic stem cells, offer the same benefits, in addition to the lack of donor site morbidity and greater self-renewal capacity. Stem cells have shown promising results in the treatment of orthopaedic conditions such as osteoarthritis, tendinopathy, tendon tears, fracture healing, osteonecrosis, and plantar fasciitis. This chapter will review the clinical implications of autologous and allogenic stem cell use in the treatment of orthopaedic injuries.

The main characteristic of a stem cell is its multipotency that has to be demonstrated experimentally as follows: I) the differentiation pathway can be characterized by specific surface receptor expression; II) it is possible to generate lineage-specific cells in vitro, and III) in a depleted organ the repopulation process can be reached in vivo. In this regard, the scientific activity to propose and improve techniques of stem cell transplant focused on its clinical application in the endocrinological field is being studied extensively. Unfortunately, not a lot is known about stem cell transplantation to cure diseases and we depend a lot on murine studies. The aim of this chapter is to review some of the most important research lines about stem cells that could have a clinical application in endocrinology.

This chapter aims to provide a short summary of the use of biological and engineering principles in wound healing applications to achieve tissue repair and regeneration. We also aim at providing the readers with a review of biomaterials, polymer-based dressing; films, hydrogels, current scaffolds, etc. used in wound healing application. Finally, the chapter aims to give information about functional dressings, bioactive matrices for wound healing and finally the chapter ends by giving information about some clinical trials and upcoming future trends.

This review article presents some mathematical models of hematopoietic cell dynamics related to bone marrow transplantation. Both allogeneic and autologous stem cell transplantations are considered. The models are expressed by threedimensional systems of ordinary differential equations whose variables stand for the abundances of healthy, leukemic and infused cells. Model parameters quantify the cellular processes of growth, cell death and sensibility to microenvironment, and cellcell interactions such as anti-host, anti-cancer and anti-graft effects. Numerical simulations and stability analysis of system equilibria are performed in order to conclude about effectiveness of transplantation procedures. In the case of allogeneic transplantation, the role of initial cell concentrations is highlighted and several therapeutic scenarios for correction of bad post-transplant evolution are suggested. The exposition is mainly based on authors' papers [3,72,75,78-80].