Frontiers in Stem Cell and Regenerative Medicine Research

Advancements in the understanding of spinal cord injury (SCI) and repair have taken great leaps in the past decade. Although understanding has evolved significantly there continues to be major limitations in the clinical interventions available for patients with spinal cord injuries. Exogenous stem cells (ExNSC) have progressed to human clinical studies, but have limitations due to ethical issues, technique and long term outcomes. However, the use of ExSCs through a stimulatory effect on growth factors, cytokine production and neurotrophic factors post injury may be beneficial. Bone marrow derived stem cells, mesenchymal stem cells, embryonic stem cells, umbilical cord stem cells, adipose derived stem cells, NSCs, Schwann cells grafts and olfactory ensheathing cells have been various types of exogenous cell types and techniques used in SCIs. The role of endogenous stem cells (eNSCs) in SCI has been promising, but still requires better lineage analyses to fully understand the responses of NSCs after SCI. It has been demonstrated that there exists a bidirectional interaction within the neuro vascular system forming the neuro vascular niche. Purinergic receptor activation was found to alter the intrinsic properties of the ependymal stem/progenitor cells enhancing regulation of proliferation, differentiation and lineage specification after a SCI. Therapies have been described using nervous tissue in combination with various synthetic bridges to overcome the structural barriers of regeneration through bypassing the injured area. More recently, newer techniques such as electrical stimulation have been described to stimulate mature neuronal differentiation. Various groups have emphasized that the glial scar is counter productive. Anderson et al. have shown the beneficial effects of a chronic glial scar in neural tissue preservation after SCI. Moreover, they have demonstrated higher levels of chondroitin sulfate proteoglycans in injured spinal cords independent of the glial scar. In sum, we have reviewed the previous and current literature on NSC and SCI to address the neurobiological utility of NSCs in spinal cord injury.

Since their development by Yamanaka in 2007, much progress has been made in the last decade toward the use of human induced pluripotent stem cells (iPSCs) in clinical practice. In this review, we will focus on the various sources of somatic cells for human iPSC generation, the methods used for generating human iPSCs, their characterization, and the progress on directed differentiation toward several cell types. We will also describe current efforts to prevent culture-driven mutations and the selection of nontumorigenic cells for clinical use. A comprehensive comparison of such methods will aid in the establishment of standardized techniques and highlight areas in which further research is still needed.

The generation of specific neuronal-lineages for cellular therapies hold great promise for nervous system disorders. Stem cells can offer regenerative and replacement therapies of the nervous system through cell signalling, which is directed by the addition of cytokines and neuronal growth factors. Adipose-derived Stem Cells (ASCs) are capable of differentiating into neuronal and glial cells through induced cell signalling pathways and altered redox status. In this chapter, we addressed the dynamic changes within ASCs in response to the changes in its milieu - a pre-requisite for transdifferentiation in vitro. We considered the functional use of ASCs as a regenerative tool in recovering neuronal cells by focusing on ligand expression and their effects on transmembrane receptors. We also discussed various levels of cell signalling capable of modifying epigenetic programming for trans-differentiation processes. Finally, we underlined the fact that harnessing of Reactive Oxygen Species (ROS) and ROSmediated cellular signalling is a secret recipe for successful differentiation of stem cells in vitro.

The skin represents the largest and most accessible organ of the body, and it is subjected to numerous aggressions such as infections, physical wounds and diseases. After a moderate-intensity injury, the intrinsic regenerative mechanisms of the skin lead to restoration of the tissue integrity. However, in some pathological cases such as chronic wounds and extensive burns, the healing capacity of the tissue is overwhelmed. In order to resolve these injuries, innovative therapies based on miRNAs as well as paracrine and trophic activities of stem cells combined with biomaterials are currently being developed. This chapter begins with a description of skin biology, followed by the main stages of wound healing including the key cells and molecules involved. Next, we describe the most studied miRNAs relevant for chronic wounds therapies and the proposed methods of delivery. Regarding cellular therapy, the main adult differentiated cells as well as stem cells available from different sources, are presented. Then, we address the commercially available skin substitutes and also the latest innovative approaches, including 3D bioprinting, for combining biomaterials with the activity of the cells previously described, in order to promote wound repair and regeneration. This chapter concludes with current challenges and future perspectives regarding the use of stem cells for skin regeneration.

Arrhythmias are electrical disturbances resulting in irregular heartbeats. Multiple ion channels orchestrate the coordinated propagation of electric stimuli within the heart. Dysfunction of the ion channels, which may result from genetic alterations in ion channel genes or their aberrant expression, can render electrical disturbances predisposing to cardiac arrhythmias. MicroRNA (miRNA) is a type of small RNA belonging to non-protein coding RNAs and is involved in RNA interference, thereby functioning as a regulator of gene expression. Recently, the role of miRNA in cardiac conduction diseases, arrhythmogenesis and their therapeutic potential has been implicated. Stem cell therapies for cardiac arrhythmia have attempted to modulate defective ionic currents by delivering engineered cells. The modulation or engineering of stem cells with appropriate miRNAs could improvise stem cell-based therapies for arrhythmia. This chapter would review the role of miRNAs in cardiac rhythmic disorders and its potential in diagnosis and treatment of cardiac arrhythmia.

In some countries, Malaria is still a challenge. The highest rates of mortality are reported in sub-Saharan Africa, where children under five years of age, pregnant women and immunocompromised patients are the most vulnerable groups. People living in these endemic areas still do not receive proper antimalarial therapy. Insecticides resistance, antimalarial drug resistance and commercialization of counterfeit and substandard antimalarials, are key factors contributing to complexity in malaria control; trying to find new alternatives to treat and control malaria, some members of the scientific community, have recently started to work in the field of stem cell therapy in experimental malaria models. The purpose of the present chapter is to make a general review concerning various aspects of the use of stem cell therapy and how these findings could improve clinical aspects during malaria pathogenesis and could be used in the field of antimalarial drug design. An overview of the effect of the parasite on the stem cells production in the host, as in hematopoiesis and in neurogenesis, is also described.