Current Stem Cell Research & Therapy - Volume 11, Issue 7, 2016

Cardiovascular cells derived from patient specific induced Pluripotent Stem Cell (iPSC) harbor gene mutations associated with the pathogenesis of inherited cardiac diseases and congenital heart diseases (CHD). Numerous reports have demonstrated the utilization of human induced Pluripotent Stem Cell (hiPSC) to model cardiac diseases as a means of investigating their underlying mechanisms. So far, they have been shown to investigate the molecular mechanisms of many cardiac disorders, such as long-QT syndrome (LQT), catecholaminergic polymorphic ventricular tachycardia (CPVT), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), LEOPARD syndrome (LS), arrhythmogenic cardiomyopathy (ACM), Friedreich ataxia (FRDA), Barth syndrome (BTHS), hypoplastic left heart syndrome (HLHS), Marfan syndrome (MFS) and other CHD. This article summarizes the growing body of research related to modeling various cardiac diseases using hiPSCs. Moreover, by reviewing the methods used in previous studies, we propose multiple novel applications of hiPSCs to investigate comprehensive cardiovascular disorders and facilitate drug discovery.

Islet transplantation is an effective therapy for severe diabetes. Nevertheless, the short supply of donor pancreases constitutes a formidable obstacle to its extensive clinical application. This shortage heightens the need for alternative sources of insulin-producing beta cells. Since mature beta cells have a very slow proliferation rate, which further declines with age, great efforts have been made to identify beta cell progenitors in the adult pancreas. However, the question whether facultative beta cell progenitors indeed exist in the adult pancreas remains largely unresolved. In the current review, we discuss the problems in past studies and review the milestone studies and recent publications.

Tissue engineering, as a frontier of medicine, is aimed at regeneration of tissue and organ which can be used for the therapy of many diseases, such as trauma, cancer, and deformity. Some pluripotent stem cells are considered to be suitable for seed cells for tissue engineering, for example, bone marrow mesenchymal stem cells, adipose-derived stem cells and epidermal stem cells. Urine-derived stem cells (USCs) have been reported, and regarded as a candidate for seed cells in tissue engineering because of low-cost collection and isolation, efficient proliferation, and multidifferentiation potential, which have been documented in recent years. In this paper, we will introduce the biological characteristics of USCs and their potential applications in tissue engineering.

Striated muscle regeneration holds an intrinsic complexity governed by many orchestrated events. When the fine balance of regulatory machineries is under strain, the homeostatic conditions are lost and degeneration starts to occur. This is the case for inherited and acquired diseases of both cardiac and skeletal muscles. A wide range of factors are currently under scrutiny for better understanding the details underlying de-/re-generation processes, of both genetic and non-genetic nature. This review focuses on three classes of non-genetic factors regulating striated muscle regeneration, i.e. microRNAs, signaling pathways and epigenetic regulators.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and it is characterized by the progressive loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Current pharmacological treatments for PD are only symptomatic and unfortunately there is still no cure for this disorder. Stem cell technology has become an attractive option to investigate and treat PD. Indeed, transplantation of fetal ventral mesencephalic cells into PD brains have provided proof of concept that cell replacement therapy can be beneficial for some patients, greatly improving their motor symptoms. However, ethical and practical aspects of tissue availability limit its widespread clinical use. Hence, the need of alternative cell sources are based on the use of different types of stem cells. Stem cell-based therapies can be beneficial by acting through several mechanisms such as cell replacement, trophic actions and modulation of inflammation. Here we review recent and current remarkable clinical studies involving stem cell-based therapy for PD and provide an overview of the different types of stem cells available nowadays, their main properties and how they are developing as a possible therapy for PD treatment.

There are an important number of neurological diseases where not neurons but glia are the responsible cells for the degeneration of the nervous system. In the last years, determinant roles for oligodendrocytes (OLs) have been demonstrated not only in myelin generation and maintenance but also for metabolic support of neurons. Oligodendroglial defects lead to brain degeneration in several diseases, supporting the idea that not only endogenous regeneration but also administration of exogenous OL precursors will lead to overcome functional deficits. In this review, we discuss many diseases where OLs play a crucial role, and focus on the different sources and methods to obtain oligodendroglial cells that could be used in cell therapy for myelin-related and oligodendrocyte-deficient diseases.

Tissue engineering has emerged as a promising scientific field potentially yielding in vitro developed tissue to replace degenerative or injured tissues in vivo, thus avoiding the donor site morbidity associated with reconstructive surgery. Integral to the process is the role of scaffolds and the biomaterials used to form them. This review explores the concept of scaffold based tissue engineering and design considerations. The scaffold needs to have certain mechanical and architectural properties, it needs to be biocompatible and biodegradable, and allow combination with bioactive molecules. We also discuss scaffolding techniques, different biomaterial options and fabrication technologies, and future areas of development.

In addition to the multi-lineage differentiation potential of mesenchymal stem cells (MSCs), studies in recent years have focused on the role of MSC paracrine in tissue regeneration. Due to their paracrine effects in damaged tissues, MSCs may be a promising therapeutic cell type in the treatment of many disorders. However, the mechanisms underlying the effects of MSC paracrine on tissue regeneration remain largely unknown, which limits the development of therapeutic applications. Stromalderived factor-1 (SDF-1) has been demonstrated to be a crucial factor that supports tissue regeneration. MSCs and damaged tissues are the main sources of SDF-1 in the regenerative microenvironment. In MSC paracrine-mediated tissue repair, SDF-1 not only acts as an important MSC-derived paracrine factor that facilitates wound healing but also improves the efficiency of MSC paracrine. In this review, we first outline the sources and regulators of SDF-1 in the regenerative microenvironment. We then summarize and discuss the current understanding of the roles of SDF-1 in MSC paracrine-mediated tissue repair, as well as its underlying mechanisms of action. Illustrating the role of SDF-1 in MSC paracrine-mediated tissue repair will facilitate a comprehensive understanding of MSC paracrine and will aid in the development of strategies to enhance the efficiency of therapies involving transplanted MSCs.

Periodontal regeneration plays an integral role in the treatment of periodontal diseases, with important clinical significance for the preservation and functional recovery of affected teeth. Periodontal ligament stem cells (PDLSCs), which were found in the periodontal ligament tissues possessing properties of pluripotency and self-renewing, could repair damaged periodontium with great promise. However, in a chronic inflammatory micro-environment, these cells suffered from reduced capacity to differentiate and regenerate. There has been a growing appreciation that tumour necrosis factor-α (TNF-α) in periodontal tissues drives cellular responses to chronic periodontitis. Several new advances, including an increased understanding of the mechanism of interaction between TNF-α and PDLSCs provides insight into inflamed cell regeneration, which in turn reveal strategies to improve the effectiveness of therapy. Here we gave a comprehensive review on the role of TNF-α in chronic periodontitis, its effect on PDLSCs differentiation and periodontal regeneration, related signaling pathways and concluded with future perspectives of research on PDLSCs-based periodontal tissue regeneration.