Promise Of Stem Cell Therapy Research Articles

Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally. This review offers a detailed analysis of stem cell applications in stroke (ischemic and hemorrhagic) recovery. It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), and Granulocyte-Colony Stimulating Factor (G-CSF) based stem cells, focusing on cell types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear Stem Cells (BMMSCs), and Neural Stem/Progenitor Cells (NSCs). The paper compiles clinical trial data to evaluate their effectiveness and safety and addresses the ethical concerns of these innovative treatments. By explaining the mechanisms of stem cell-induced neurological repair, this review underscores stem cells' potential in revolutionizing stroke rehabilitation and suggests avenues for future research.

Beyond Repair: The Science and Promise of Stem Cell Therapy

Beyond Repair: The Science and Promise of Stem Cell Therapy

The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration.

Cartilage injury and degeneration are hallmarks of osteoarthritis (OA), the most common joint disease. OA is a major contributor to pain, loss of function, and reduced quality of life. Over the last decade, considerable research efforts have focused on cell-based therapies, including several stem cell-derived approaches to reverse the cartilage alterations associated with OA. Although several tissue sources for deriving cell-based therapies have been identified, none of the resident stem cell populations have adequately fulfilled the promise of curing OA. Indeed, many cell products do not contain true stem cells. As well, issues with aggressive marketing efforts, combined with a lack of evidence regarding efficacy, lead the several national regulatory bodies to discontinue the use of stem cell therapy for OA until more robust evidence becomes available. A review of the evidence is timely to address the status of cell-based cartilage regeneration. The promise of stem cell therapy is not new and has been used successfully to treat non-arthritic diseases, such as hematopoietic and muscle disorders. These fields of regenerative therapy have the advantage of a considerable foundation of knowledge in the area of stem cell repair mechanisms, the role of the stem cell niche, and niche-supporting cells. This foundation is lacking in the field of cartilage repair. So, where should we look for the ideal stem cell to regenerate cartilage? It has recently been discovered that cartilage itself may contain a population of SC-like progenitors. Other potential tissues include stem cell-rich dental pulp and the adolescent growth plate, the latter of which contains chondrocyte progenitors essential for producing the cartilage scaffold needed for bone growth. In this article, we review the progress on stem cell therapies for arthritic disorders, focusing on the various stem cell populations previously used for cartilage regeneration, successful cases of stem cell therapies in muscle and hemopoietic disorders, some of the reasons why these other fields have been successful (i.e., “lessons learned” to be applied to OA stem cell therapy), and finally, novel potential sources of stem cells for regenerating damaged cartilage in vivo.

IL-6 coaxes cellular dedifferentiation as a pro-regenerative intermediate that contributes to pericardial ADSC-induced cardiac repair

BackgroundCellular dedifferentiation is a regenerative prerequisite that warrants cell cycle reentry and appropriate mitotic division during de novo formation of cardiomyocytes. In the light of our previous finding that expression of injury-responsive element, Wilms Tumor factor 1 (WT1), in pericardial adipose stromal cells (ADSC) conferred a compelling reparative activity with concomitant IL-6 upregulation, we then aim to unravel the mechanistic network that governs the process of regenerative dedifferentiation after ADSC-based therapy.Methods and resultsWT1-expressing ADSC (eGFP:WT1) were irreversibly labeled in transgenic mice (WT1-iCre/Gt(ROSA)26Sor-eGFP) primed with myocardial infarction. EGFP:WT1 cells were enzymatically isolated from the pericardial adipose tissue and cytometrically purified (ADSCgfp+). Bulk RNA-seq revealed upregulation of cardiac-related genes and trophic factors in ADSCgfp+ subset, of which IL-6 was most abundant as compared to non-WT1 ADSC (ADSCgfp−). Injection of ADSCgfp+ subset into the infarcted hearts yielded striking structural repair and functional improvement in comparison to ADSCgfp− subset. Notably, ADSCgfp+ injection triggered significant quantity of dedifferentiated cardiomyocytes recognized as round-sharp, marginalization of sarcomeric proteins, expression of molecular signature of non-myogenic genes (Vimentin, RunX1), and proliferative markers (Ki-67, Aurora B and pH3). In the cultured neonatal cardiomyocytes, spontaneous dedifferentiation was accelerated by adding tissue extracts from the ADSC-treated hearts, which was neutralized by IL-6 antibody. Genetical lack of IL-6 in ADSC dampened cardiac dedifferentiation and reparative activity.ConclusionsTaken collectively, our results revealed a previous unappreciated effect of IL-6 on cardiac dedifferentiation and regeneration. The finding, therefore, fulfills the promise of stem cell therapy and may represent an innovative strategy in the treatment of ischemic heart disease.

Inducible Pluripotent Stem Cells as a Potential Cure for Diabetes.

Over the last century, diabetes has been treated with subcutaneous insulin, a discovery that enabled patients to forego death from hyperglycemia. Despite novel insulin formulations, patients with diabetes continue to suffer morbidity and mortality with unsustainable costs to the health care system. Continuous glucose monitoring, wearable insulin pumps, and closed-loop artificial pancreas systems represent an advance, but still fail to recreate physiologic euglycemia and are not universally available. Islet cell transplantation has evolved into a successful modality for treating a subset of patients with ‘brittle’ diabetes but is limited by organ donor supply and immunosuppression requirements. A novel approach involves generating autologous or immune-protected islet cells for transplant from inducible pluripotent stem cells to eliminate detrimental immune responses and organ supply limitations. In this review, we briefly discuss novel mechanisms for subcutaneous insulin delivery and define their shortfalls. We describe embryological development and physiology of islets to better understand their role in glycemic control and, finally, discuss cell-based therapies for diabetes and barriers to widespread use. In response to these barriers, we present the promise of stem cell therapy, and review the current gaps requiring solutions to enable widespread use of stem cells as a potential cure for diabetes.

Structured nanofilms comprising Laponite® and bone extracellular matrix for osteogenic differentiation of skeletal progenitor cells.

Functionalized scaffolds hold promise for stem cell therapy by controlling stem cell fate and differentiation potential. Here, we have examined the potential of a 2-dimensional (2D) scaffold to stimulate bone regeneration. Solubilized extracellular matrix (ECM) from human bone tissue contains native extracellular cues for human skeletal cells that facilitate osteogenic differentiation. However, human bone ECM displays limited mechanical strength and degradation stability under physiological conditions, necessitating modification of the physical properties of ECM before it can be considered for tissue engineering applications. To increase the mechanical stability of ECM, we explored the potential of synthetic Laponite® (LAP) clay as a counter material to prepare a 2D scaffold using Layer-by-Layer (LbL) self-assembly. The LAP and ECM multilayer nanofilms (ECM/LAP film) were successfully generated through electrostatic and protein-clay interactions. Furthermore, to enhance the mechanical properties of the ECM/LAP film, application of a NaCl solution wash step, instead of deionized water following LAP deposition resulted in the generation of stable, multi-stacked LAP layers which displayed enhanced mechanical properties able to sustain human skeletal progenitor cell growth. The ECM/LAP films were not cytotoxic and, critically, showed enhanced osteogenic differentiation potential as a consequence of the synergistic effects of ECM and LAP. In summary, we demonstrate the fabrication of a novel ECM/LAP nanofilm layer material with potential application in hard tissue engineering.

Immunomodulatory Effect of Urine-derived Stem Cells on Inflammatory Bowel Diseases via Downregulating Th1/Th17 Immune Responses in a PGE2-dependent Manner.

Despite the therapeutic promise of stem cell therapy in the treatment of inflammatory bowel diseases [IBD], most donor cell populations have to be obtained via invasive approaches and often remain insufficiently validated. Urine-derived stem cells [USC] were recently shown to have regenerative properties and can be harvested in a safe, low-cost, and noninvasive way. This study aims to evaluate the immunomodulatory effect of USC and their efficacy in the management of IBD. Human USC were isolated and expanded from the urine of healthy male adult volunteers [n = 3, age range 24-30 years]. USC were characterised by cell surface marker expression profile and multipotent differentiation. The in vitro immunomodulatory effect of USC was evaluated by co-culturing with human CD4+ T cells upon stimulation with phytohaemagglutinin [PHA]. The proliferation of CD4+ T was measured by fluorescence-activated cell sorting [FACS]. Cytokine array and quantitative real-time polymerase chain reaction [RT-PCR] were applied to examine cytokine levels. In vivo therapeutic value of USC was assessed using a murine colitis model induced by dextran sulphate sodium [DSS] or 2, 4, 6-trinitrobenzene sulphonic acid [TNBS]. The immunomodulatory effect of USC and bone marrow-derived mesenchymal stem cells [BMSC] was compared when co-cultured with CD4+ T cells. The therapeutic efficacy of USC and BMSC on IBD was compared when administered in an acute DSS model in vivo. USC were positive for mesenchymal stem cell markers but were negative for haematopoietic stem cell markers. These cells differentiated into osteo-, adipo-, and chondrogenic cell lineages. Similar to BMSC, the proliferation of CD4+ T cells was significantly inhibited when co-cultured with USC, as a consequence of Th1/Th17 immune response inhibition. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in both acute and chronic murine colitis models. Moreover, implantation of USC led to downregulation of the Th1/Th17 immune responses in a PGE2-dependent manner. This study demonstrated that implantation of USC reduces inflammation in an IBD rodent model via downregulation of Th1/Th17 immune responses, indicating that USC therapy serves as a potential cell-based therapeutic candidate treatment for IBD.

Evolving Visions for Global Stem Cell Institutes

Evolving Visions for Global Stem Cell Institutes

Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress.

Survival of mesenchymal stem cells (MSCs) against oxidative stress and inflammation is vital for effective stem cell therapy. The reactive oxygen species (ROS) result in apoptosis and release of inflammatory mediators. Adipose-derived stem cells (ASCs) have shown promise for stem cell therapy owing to their anti-inflammatory and anti-oxidant activity. Previously, we showed the benefits of vitamin E against hydrogen peroxide (H2O2)-induced oxidative stress in rat bone marrow-derived MSCs. In this study, we aim to evaluate the effect of vitamin E treatment on porcine adipose-derived mesenchymal stem cells (pASCs) against H2O2-induced oxidative stress. The oxidative stress was induced by treating pASCs with 500μM H2O2 with or without vitamin E. Viability of pASCs is enhanced after vitamin E treatment. In addition, reduced cellular toxicity, total NO level, PGE2 production and caspase-3 activity were observed after vitamin E treatment. Gene expression analysis of vitamin E-treated pASCs showed down-regulated expression for the genes associated with oxidative stress and apoptosis, viz., NOS2, Casp3, p53, BAX, MDM2, NFκB, HIF1α and VEGF-A genes. On the other hand, expression of anti-apoptotic and survival genes was up-regulated, viz., BCL2, BCL2L1 and MCL1. Furthermore, phosphorylation of Akt was attenuated following vitamin E treatment. The findings of this study may help in developing effective stem cell therapy for the diseases characterized by the oxidative stress and inflammation.

Emerging Therapies for Congestive Heart Failure.

The treatment of atherosclerotic heart disease has improved remarkably over the last several decades; however, the outlook for patients with symptomatic congestive heart failure with reduced ejection fraction remains bleak. Current drug therapies target the neurohormonal activation that accompanies congestive heart failure, but do not address the fundamental pathology inherent in this condition-the loss of contractile capacity. Stem cell therapies offer the possibility of rectifying this deficiency and normalizing left ventricular dimensions and cardiac performance by regenerating novel contractile tissue, thereby reversing the negative remodeling that portends progressive left ventricular dysfunction, worsening symptoms, and ultimately cardiogenic shock. Here we review the promise of stem cell therapies in the treatment of heart failure with reduced ejection fraction, the current state of clinical developments, and briefly comment on the future of the field.

Stem Cell Therapy for Heart Failure Is Promoted Directly to Consumers

Despite the theoretical promise of stem cell therapy for heart failure (HF), the treatment has not been efficacious in clinical trials and has not been

Is Human Embryonic Stem Cell (HESC) Research Still Necessary Today?

Given the promise of stem cell therapies, scientists throughout the world are conducting stem cell research using various kinds of stem cells including human embryonic stem cells (HESC). However, HESC research is very controversial in some societies as the extraction of stem cells involves the destruction of the human embryo. The ethical concerns of this kind of research have led scientists to search for other methods to derive stem cells that do not involve the destruction of embryos. These different types of stem cell research are said to sidestep the ethical dilemma associated with HESC research and so are considered as ethically acceptable ways to obtain stem cells; possibly, they may even mark the end of HESC research. However, each of these stem cell methods presents its own challenges, scientific and ethical, as this article explores. This paper examines the impact of the emergence of different types of stem cell research and discusses whether it is still necessary for scientists to conduct the contentious HESC research.

Current concepts in the use of stem cells for the treatment of spinal cord injury

Following spinal cord injury, significant losses in the neural and stromal structures occur. This event contributes to the development of scar tissue that may hinder or prevent the regeneration and formation of functional neural tissue. The regenerative potential of stem cells to reverse or prevent the progression of neural injury has driven substantial interest in their clinical application. The aim of this article is to review the current understanding regarding the promise of stem cell therapy in the setting of spinal cord injuries.

THE INFLUENCE OF NICOTINAMIDE ON THE DEVELOPMENT OF NEURONS

A major challenge in translating the promise of stem cell therapies to treat a myriad of neurodegenerative disorders is to rapidly and efficiently direct pluripotent stem cells to generate differentiated neurons. The application of active vitamin metabolites known to function in embryonic development and maintenance in the adult brain such as retinoic acid (vitamin A), ascorbic acid (vitamin C) and calcitriol (vitamin D3) have proven effective in current in-vitro differentiation protocols. Therefore, in this study we investigated whether the biologically active vitamin B3 metabolite, nicotinamide could enhance the differentiation of mouse embryonic stem cells, cultured as monolayers, into mature neurons at either early or late stages of development. Interestingly, nicotinamide elicited a dose-responsive increase in the percentage of neurons when added at an early developmental stage to the cells undergoing differentiation (days 0–7). Nicotinamide (10 mM) increased the proportion of β-III tubulin positive neurons by two fold and concomitantly decreased the total number of cells in culture, measured by quantification of 4′, 6-diamidino-2-phenylindole positive cells. This effect could result from induction of cell-cycle exit and/or selective cell death in non-neural populations. Higher levels of nicotinamide (20 mM) induced cytoxicity and cell death. This study supports previous evidence that vitamins and their metabolites can efficiently direct stem cells into neurons. Current work is focusing on the effect of nicotinamide on the process of neural induction and whether nicotinamide influences the generation of particular neuronal subtypes implicated in neurodegenerative diseases, specifically focusing on midbrain dopamine neurons; towards a therapy for Parkinson9s disease.

Pediatric Stem Cells ...............The future ahead

Stem cell therapy has been used around the world to treat life threatening conditions, and the full promise of stem cell therapy has only been glimpsed so far. Discoveries in stem cell research presents an opportunity for scientific evidences that stem cells, whether derived from adult tissues or the earliest cellular forms hold great promise that go far beyond regenerative medicine.Pediatric stem cells or SHED are found in the exfoliated deciduous/ primary teeth of children. Recent studies show that SHED appear to have the ability to develop into more types of body tissue than other types of stem cells. This difference opens the door to more therapeutic applications .There is much research left to be conducted, but the existing research has clearly shown that primary teeth are a better source for stem cells. While the promise of the immense scope and magnitude that stem cell therapies will have upon the population will only be fully realized in the future, Dental Professionals have realized that the critical time to act is now. The available opportunities to bank their patients dental stem cells will have the greatest future impact if seized while patients are young and healthy.

Quantification of Human Neural Stem Cell Fate Using Volocity® 3D Image Analysis Software

The promise of stem cell therapy offers hope for the treatment of many human diseases and injuries. Spinal cord and traumatic brain injuries can cause the loss of neurons and glial cells. These lost cells may be partially replaced by transplanting multipotent human neural stem cells (hNSCs), which can differentiate into specialized neural cell types. The potential for these remarkable cells to promote recovery of neural function has made them a strong focus of researchers in this field.

Cell therapy for multiple sclerosis.

The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

The continued promise of stem cell therapy in regenerative medicine

The use of stem cells is galvanizing regenerative medicine research. An analysis of recent trends as typified by articles published between 2009 and 2010 in the journals Cell Transplantation--The Regenerative Medicine Journal and Medical Science Monitor demonstrate the increasing importance of stem cell research as being on the cutting edge of regenerative medicine research. The analysis revealed an even split between transplantation and non-transplantation studies, showing that both the applicability and general research is being pursued. New methods and tissue engineering are also highly important components of regenerative medicine as demonstrated by a number of the stem cell studies being involved with either ex vivo manipulation, or cotransplantation with other cells or biomaterials. This suggests that the best results may be achieved with adjuvant therapies. The non-transplantation studies were more focused on manipulation of transplantable agents including cells and scaffold systems, as well as the use of medicines and dietary supplements. The further elucidation of disease mechanisms was a major contribution. This analysis suggests that regenerative medicine is proceeding at a rapid pace and the next few years should be of considerable interest with the initial results of pioneering stem cell therapies being announced.

Mesenchymal stem cells for bone repair and metabolic bone diseases.

Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.

A importância do uso das células tronco para a saúde pública

Stem cells were elected 'Breakthrough of the Year' by Science(1) magazine in 1999, having shown that stem cells from adult tissues retained the ability to differentiate into other tissue types. During the previous year, the first human embryo stem cell lines were established. Since then, the number of scientific papers on stem cells has been increasing exponentially, establishing new paradigms that are rapidly challenged by subsequent experiments. This paper reviews the stem cell research field, divided into two groups: embryo and adult stem cells. While the differentiation potential of the former is well characterized in mice and humans, their use in cell therapy and research has been hampered by histocompatibility, safety and ethical issues. In contrast, adult stem cells do not present these problems. However, the extent of their plasticity is still under investigation. Nevertheless, numerous clinical trials in humans are under way, mainly with stem cells derived from bone marrow. This paper discusses discuss the importance of working with both classes of human stem cells in order to fulfill the promise of stem cell therapies.