Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

Type 1 diabetes mellitus (T1DM) is a complex multifactorial disorder which involves a loss of self-tolerance leading to the autoimmune destruction of pancreatic β−cells. Exogenous insulin administration cannot mimic precise pancreatic β-cell regulation of glucose homeostasis, thereby leading to severe long-term complications. Pancreas or islet transplant only provides partial exogenous insulin independence and induces several adverse effects, including increased morbidity and mortality. The scientific community and diabetic patients are thus, still waiting for an effective therapy which could preserve the remaining β-cells, replenish islet mass and protect newly-generated β-cells from autoimmune destruction. Mesenchymal stem cells (MSCs) have been envisioned as a promising tool for T1DM treatment over the past few years, since they could differentiate into glucose-responsive insulin-producing cells. Their immunomodulatory and proangiogenic roles can be used to help arrest β-cell destruction, preserve residual β-cell mass, facilitate endogenous β-cell regeneration and prevent disease recurrence, thereby making them ideal candidates for the comprehensive treatment of diabetic patients. This review focuses on recent pre-clinical data supporting MSC use in regenerating β-cell mass and also in treating several T1DM-associated complications. Clinical trial results and the ongoing obstacles which must be addressed regarding the widespread use of such therapy are also discussed.Fil: Ezquer, Marcelo. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Arango Rodriguez, Martha. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Giraud Billoud, Maximiliano German. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ezquer, Fernando. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; Chil

Approaches in the treatment of Parkinson\u27s disease : a focus on stem cell-based therapies.

Parkinson\u27s disease (PD) is a hypokinetic movement disorder resulting from the progressive neurodegeneration of the dopaminergic nigrostriatal system in the brain and the resulting imbalance between dopamine and acetylcholine in the basal ganglia motor circuitry. Although drug-based therapy approaches have shown dramatic symptomatic improvement in patients, they do not halt the progressive nature of the disease and their long-term use is associated with distressing adverse side effects. Consequently, several studies have aimed at discovering effective non-pharmacological strategies to reduce or to eliminate the need for drugs and possibly to halt or to reverse the neurodegenerative process in PD. Surgical deep brain stimulation, neurotrophic factor delivery, gene therapy and cell replacement therapy are potential candidates. Here, we review the latest advancements in the aforementioned therapeutic strategies paying special attention to regenerative stem cell- (SC)-based approaches in combating PD. Although intracerebrally transplanted SC-derived cells can replace degenerated neurons in PD and simultaneously secrete neurotrophic factors that can partly protect the viable ones, potential tumorigenicity and low survivability of these cells hinder the advancement of this novel therapeutic approach. Hence, more investigations are needed to resolve the associated safety and efficacy concerns in order to make SC-based therapy a feasible therapy for PD patients

The Use of stem cells in burns treatment

Introduction and purpose: Burns are a real problem that can result in long hospitalization and scarring. Stem cells (SCs) have been shown to have a number of actions that accelerate and improve the healing process. The aim of this review is to explore the stem cell mechanisms that can be used to improve burn healing Materials and methods: A comprehensive analysis of articles available on PubMed and Google Scholar was undertaken by entering keywords in appropriate configuration: Stem cells/  burn wound/ wound healing/  mesenchymal stem cells. Description of the state of knowledge: In the physiological process of wound healing, migration and proliferation of stem cells initiate epithelialization. The therapeutic use of stem cells has many beneficial effects. Their regenerative potential is superior to conventional treatments. Stem cells due to their ability to differentiate, autocrine and paracrine activity and immunomodulatory activity -  accelerate the wound healing process, promote cell proliferation, collagen production, regulate inflammation, prevent hypertrophic scarring, stimulate re-epithelialization, angiogenesis and granulation. Conclusion: The mechanisms of action of stem cells appears to be promising in the context of treating burn wounds, but in order for them to fully replace current treatments, a deeper understanding of the complex biological mechanisms and further studies are needed to evaluate the efficacy and safety of different types of stem cells and to identify the most suitable ones

The light and shadow of senescence and inflammation in cardiovascular pathology and regenerative medicine

Recent epidemiologic studies evidence a dramatic increase of cardiovascular diseases, especially associated with the aging of the world population. During aging, the progressive impairment of the cardiovascular functions results from the compromised tissue abilities to protect the heart against stress. At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. In this review, we explore the intrinsic and extrinsic causes of cellular senescence and their role in the onset of these cardiovascular pathologies. Additionally, we dissect the effects of aging on the cardiac endogenous and exogenous reservoirs of stem cells. Finally, we offer an overview on the strategies of regenerative medicine that have been advanced in the quest for heart rejuvenation

From DMEK to Corneal Endothelial Cell Therapy: Technical and Biological Aspects

The main treatment available for restoration of the corneal endothelium is keratoplasty and DMEK provides faster visual recovery and better postoperative visual acuity when compared to DSAEK. However, the technical challenges related to this technique and the steep technical learning curve seem to prevent the overcoming of DSAEK in favor of DMEK. Furthermore, the outcome of lamellar keratoplasty techniques is influenced by problems related to corneal grafting tissue availability, management, and quality. On the other hand, improvements in the field of cell engineering have opened the way for the use of stem cells-derived corneal endothelial cells with regenerative intent. In this overview, latest findings in endothelial cell engineering are reported, and perspectives of clinical application of mesenchymal stem cells for corneal endothelial replacement and regeneration are evaluated

Human adipose-derived stem cells: current challenges and clinical perspectives

Adult or somatic stem cells hold great promise for tissue regeneration. Currently, one major scientific interest is focused on the basic biology and clinical application of mesenchymal stem cells. Adipose tissue-derived stem cells share similar characteristics with bone marrow mesenchymal stem cells, but have some advantages including harvesting through a less invasive surgical procedure. Moreover, adipose tissue-derived stem cells have the potential to differentiate into cells of mesodermal origin, such as adipocytes, cartilage, bone, and skeletal muscle, as well as cells of non-mesodermal lineage, such as hepatocytes, pancreatic endocrine cells, neurons, cardiomyocytes, and vascular endothelial cells. There are, however, inconsistencies in the scientific literature regarding methods for harvesting adipose tissue and for isolating, characterizing and handling adipose tissue-derived stem cells. Future clinical applications of adipose tissue-derived stem cells rely on more defined and widespread methods for obtaining cells of clinical grade quality. In this review, current methods in adipose tissue-derived stem cell research are discussed with emphasis on strategies designed for future applications in regenerative medicine and possible challenges along the way.As células-tronco adultas ou somáticas detêm grande promessa para a reparação e regeneração de tecidos. Atualmente, o interesse dos cientistas é contínuo na investigação da biologia de células-tronco mesenquimais, tanto em aspectos básicos, quanto no potencial de aplicações terapêuticas. As células-tronco adultas derivadas do estroma do tecido adiposo, em comparação com as células-tronco derivadas do estroma da medula óssea, apresentam como vantagem o método fácil de obtenção da fonte tecidual. As células-tronco adultas derivadas do estroma do tecido adiposo apresentam potencial para se diferenciarem em células de tecidos mesodérmicos, como os adipócitos, as cartilagens, os ossos e o músculo esquelético e não mesodérmicos, como os hepatócitos, as células pancreáticas endócrinas, os neurônios, os hepatócitos e as células endoteliais vasculares. Entretanto, os dados disponíveis na literatura científica sobre as características das células-tronco adultas derivadas do estroma do tecido adiposo e os procedimentos para sua obtenção e manipulação no laboratório são inconsistentes. É necessário o desenvolvimento de metodologias e procedimentos eficazes de isolamento dessas células para obtenção de células em quantidade e qualidade suficientes para aplicação terapêutica. Nesta revisão, são discutidos os métodos correntes de coleta de tecido adiposo, isolamento e caracterização de células-tronco adultas derivadas do estroma do tecido adiposo, com ênfase na futura aplicação em medicina regenerativa e nos possíveis desafios nesse recente campo da ciência.Universidade Federal do Vale do São FranciscoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Neurologia e NeurocirurgiaUNIFESP, EPM, Depto. de PatologiaUNIFESP, Depto. de Neurologia e NeurocirurgiaSciEL

Rationale and Methodology of Reprogramming for Generation of Induced Pluripotent Stem Cells and Induced Neural Progenitor Cells.

Great progress has been made regarding the capabilities to modify somatic cell fate ever since the technology for generation of induced pluripotent stem cells (iPSCs) was discovered in 2006. Later, induced neural progenitor cells (iNPCs) were generated from mouse and human cells, bypassing some of the concerns and risks of using iPSCs in neuroscience applications. To overcome the limitation of viral vector induced reprogramming, bioactive small molecules (SM) have been explored to enhance the efficiency of reprogramming or even replace transcription factors (TFs), making the reprogrammed cells more amenable to clinical application. The chemical induced reprogramming process is a simple process from a technical perspective, but the choice of SM at each step is vital during the procedure. The mechanisms underlying cell transdifferentiation are still poorly understood, although, several experimental data and insights have indicated the rationale of cell reprogramming. The process begins with the forced expression of specific TFs or activation/inhibition of cell signaling pathways by bioactive chemicals in defined culture condition, which initiates the further reactivation of endogenous gene program and an optimal stoichiometric expression of the endogenous pluri- or multi-potency genes, and finally leads to the birth of reprogrammed cells such as iPSCs and iNPCs. In this review, we first outline the rationale and discuss the methodology of iPSCs and iNPCs in a stepwise manner; and then we also discuss the chemical-based reprogramming of iPSCs and iNPCs

Comparative characteristics of human stem cells

Stem cell therapy is one of the most perspective methods of clinical medicine; SC-containing products are actively investigated in clinical trials, while some of them are already officially approved for treatment in many countries worldwide. The purpose of this review is to perform comparative analysis of stem cell types, methods of their procurement and perspectives of their employment. Stem cells (SCs) could be divided into groups according to the age of the donor organism. Embryonic SCs are isolated from blastocyst, obtained as a result of extracorporeal fertilization, cloning, semicloning or parthenogenesis (androgenetic and gynogenetic SCs). Fetal SCs could be isolated from embryonic and fetal tissues before the birth or from miscarriages and abortion material (including ectopic pregnancy). Among fetal there is and especial group of perinatal extraembryonic SCs which are obtained from extraembryonic organs (umbilical cord, amnion, placenta) after the birth; among them hematopoietic, mesenchymal, epithelial and decidual cells are distinguished. Adult (somatic, tissue specific) SCs could be isolated from different tissues and organs of adult organism throughout the life; their properties depend on the place of their localization and age of the donor. Additionally, SCs could be created artificially from mature cells by modification of gene expression; they are united in the group of induced pluripotent SCs. Every group of SCs is not homogenous and has its advances and drawbacks are analyzed in this review. Also, application of exosomes, microvesicles and apoptotic bodies produced by stem cells as an alternative of cellular therapy is considered

Cellular Transplantation-Based Therapeutic Strategies for Spinal Cord Injuries: Preclinical and Clinical Updates

Spinal cord injury (SCI) is a distressing neurological condition that causes loss of neural tissue, with subsequent damages to neural circuitry, and loss of sensorimotor function. The SCIs have an estimated incidence rate of ~80 cases per million populations. Till date, no ratified effective therapeutic strategy for SCIs exist; however, recent advancements in regenerative medicines to protect and regenerate damaged/lost neural tissues following SCIs have shown promising results in preclinical and clinical trials. Moreover, there is a greater need to fully understand underlying mechanisms following cellular transplantation that can be achieved through proper differentiation of desired cell type, and their in-vivo tracking of migration, proliferation and integration into the host system. Furthermore, techniques that can prevent teratomas formation following cellular transplantation have been reported. In addition to the ongoing comprehensive neuroregenerative and neuroprotective therapeutic strategies for SCIs, novel technologies are emerging including neuroscience-based computational and robotic rehabilitational therapies. These improved strategies in combination with cell-based therapeutic approaches are opening new avenues for future research to completely cure SCIs. Herein, we intended to review pathophysiological mechanisms following SCI, preclinical and clinical updates of cellular transplantation, the extent of success from these transplantations, associated controversies and other emerging technologies