Use Of Stem Cell Therapy Research Articles

Embryonic stem cell therapy applications for autoimmune, cardiovascular, and neurological diseases: A review

Parkinson’s disease, type 1 diabetes, and coronary artery disease are some of the few difficult diseases to control. As a result, there has been pressure in the scientific community to develop new technologies and techniques that can treat, or ultimately cure these life-threatening diseases. One such scientific advancement in bridging the gap is the use of stem cell therapy. In recent years, stem cell therapy has gained the spotlight in becoming a possible intervention for combating chronic diseases due to their unique ability to differentiate into almost any cell line. More precisely, embryonic stem cell therapy may hold the potential for becoming the ideal treatment for a multitude of diseases as embryonic stem cells are not limited in their ability to differentiate like their counterpart adult stem cells. Although there has been controversy around the usage of embryonic stem cells, there has been found a great deal of potential within the usage of these cells to treat a multitude of life-threatening diseases. In this article, we will break down the categories of diseases in which embryonic stem cell therapy can be applied into: autoimmune, neurological, and cardiovascular with three diseases relating to each category. Our aim is to provide a comprehensive review on the advantages of embryonic stem cells (ESCs) that can solve current obstacles and push advances towards stem cell therapies in the field for the most common diseases.

Laboratory Training Guidelines for Clinicians Undertaking Stem Cell Therapy

Stem cell-based regenerative therapies are an exciting and emerging field in medicine and dentistry. Since the 1960s, stem cell therapies have been successfully performed and approved in the form of bone marrow transplants and more recently, in skin and corneal grafting. However, the field of regenerative cell therapy has somewhat come to a halt due to safety, ethical and legal concerns associated with medical and scientific practices. In Australia, stem cell therapies, besides those mentioned above, are permitted provided that they are autologous in nature and that the procedure is performed by or under the supervision of a registered medical practitioner in a single treatment. However, the medical practitioner requires no formal stem cell training. We have identified this deficiency in optimal patient care and propose that education in the safe, legal and ethical delivery of stem cell treatments be part of a mandatory training course for medical/dental practitioners and the scientific team prior to the clinical use of stem cell therapies in Australia, and arguably, on a global scale. This involves the scientific and medical team having a sound understanding of the biology of stem cells, their appropriate applications and basic validation and laboratory techniques in order to provide effective and safe treatment for improved patient outcomes. As such, this article aims to propose a frame-work of scientific guidelines for dental and medical practitioners to undertake stem cell therapies.

The Use of Stem Cell Therapy to Reverse Opioid Tolerance.

Opioid tolerance (OT) and opioid-induced hyperalgesia (OIH) are major challenges in medicine. Here we report that transplantation of mesenchymal stem cells (MSCs) prevented and reversed OT and OIH in rats and mice. The preventive and therapeutic effects were long-lasting and consistent across different assessment schemes. Both intrathecal and intravenous transplantations were effective and safe. This emerging therapeutic strategy has thus shown promise to impact clinical practice and improve the efficacy and safety of opioid therapy.

The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective.

The use of stem-cell therapies for the treatment of various musculoskeletal conditions, especially knee osteoarthritis (OA), is rapidly expanding, despite only low-level evidence to support its use. Centers offering these therapies are often marketing and charging patients out-of-pocket costs for such services. Therefore, the purpose of this study was to determine the current marketed: (1) prices and (2) clinical efficacy of stem-cell therapies for knee OA. This was a prospective cross-sectional study which queried 317 U.S. centers that offered direct-to-consumer stem-cell therapies for musculoskeletal conditions. A total of 273 of 317 centers were successfully contacted via phone or e-mail, using a simulated 57-year-old male patient with knee OA. Scripted questions were asked by the simulated patient to determine the marketed prices and clinical efficacy. Centers generally reported the proportion of patients who had "good results" or "symptomatic improvement." The mean price of a unilateral (same-day) stem-cell knee injection was $5,156 with a standard deviation of $2,446 (95% confidence interval [CI]: $4,550-5,762, n = 65). The mean proportion of claimed clinical efficacy was 82% with a standard deviation of 9.6% (95% CI: 79.0-85.5%, n = 36). Most American stem-cell centers offer therapies for knee OA. The cost of these therapies averages about $5,000 per injection, and centers claim that 80% of the patients had "good results" or "symptomatic improvement," denoting a gap between what is documented in the published literature and the marketing claims. These findings offer both patients and physicians insight into the current stem-cell market for knee OA. We hope that with this information, providers can more optimally make patients aware of discrepancies between what is being marketed versus the current evidence-based landscape of these therapies for knee OA.

Electrical Guidance of Human Stem Cells in the Rat Brain.

SummaryLimited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

Stem cells applications in bone and tooth repair and regeneration: New insights, tools, and hopes.

The exploration of stem and progenitor cells holds promise for advancing our understanding of the biology of tissue repair and regeneration mechanisms after injury. This will also help in the future use of stem cell therapy for the development of regenerative medicine approaches for the treatment of different tissue-species defects or disorders such as bone, cartilages, and tooth defects or disorders. Bone is a specialized connective tissue, with mineralized extracellular components that provide bones with both strength and rigidity, and thus enable bones to function in body mechanical supports and necessary locomotion process. New insights have been added to the use of different types of stem cells in bone and tooth defects over the last few years. In this concise review, we briefly describe bone structure as well as summarize recent research progress and accumulated information regarding the osteogenic differentiation of stem cells, as well as stem cell contributions to bone repair/regeneration, bone defects or disorders, and both restoration and regeneration of bones and cartilages. We also discuss advances in the osteogenic differentiation and bone regeneration of dental and periodontal stem cells as well as in stem cell contributions to dentine regeneration and tooth engineering.

Literature Review to Optimize the Autologous Fat Transplantation Procedure and Recent Technologies to Improve Graft Viability and Overall Outcome: A Systematic and Retrospective Analytic Approach.

Investigation and evaluation of the current methods and steps of autologous fat transplantation to optimize the viability of fat grafts and procedure outcome in quest of a more standardized protocol. A thorough literature search was performed across the CNKI, Wan Fang, PubMed, Ovid and EMBASE databases from the year 1970 to December 2014, collecting and classifying all of the autologous fat transplantation-related reports and articles, and after screening, a critical retrospective analysis was performed on the included data. A total of 65 articles were included in the study. However, there were limited numbers of cases dealing with procedure-related steps such as the selection of donor sites, fat acquisition, graft treatment and methodology of transplant, resulting in a significant lack of evidence support, furthermore urging the need for more standardized protocol for the steps of autologous fat transplant to improve graft viability and overall outcome while decreasing procedure-related morbidity. No good evidence was obtained to optimize the donor site, acquisition, processing and transplantation steps of the whole process of autologous fat transplantation. Tissue engineering and stem cell research have the potential to revolutionize the future of reconstructive surgery by replacing tissue, obviating the need for donor site morbidity. However, the use of stem cell therapies to expand and grow tissue for reconstruction must occur in the context of risk management. Balancing ease of harvest with yield and efficacy has been a delicate and often difficult trade-off which has prompted the scientific community to investigate alternative sources. However, there is much hope in the evaluation and implementation of multimodality approaches for autologous fat transplant, including thriving technologies such as ultrasound-assisted, water jet-assisted, nanotechnology-assisted liposuction in combination with revolutionary fat treatment technologies such as the VASER system. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

No evidence for the use of stem cell therapy for tendon disorders: a systematic review

IntroductionStem cells have emerged as a new treatment option for tendon disorders. We systematically reviewed the current evidence for stem cell therapy in tendon disorders.MethodsRandomised and non-randomised controlled trials, cohort...

Bone Marrow Stem Cell Therapy (SCT) for Peripheral Arterial Disease (PAD): an Initial Experience

Introduction: 30% of patients with critical limb ischaemia (CLI) are not suitable for conventional treatment. Use of stem cell therapy (SCT) is relatively new. This study shares an initial experience using SCT in 4 patients. Methods: Approval from Institutional Medical Board Ethics Committee was obtained prior to commencement and informed consent was sought. Patients included had extensive CLI history that was no longer amenable to standard treatment. Bone marrow aspiration from the iliac crest was carried out under regional anaesthesia. This was later centrifuged and injected intramuscularly and adjacent to affected vessels. Wound surveillance was then performed. Results: SCT was well tolerated in all 4 patients and 2 had favourable results. None developed related complications. Patients 1 and 2 showed improvement of rest pain, claudication symptoms and healing of ulcers. Angiogenesis and neovascularization can be seen in follow up angiography for patient 1. Wound healing was not noted in the other 2 patients, with both requiring amputations eventually. Discussion: The experience while early has been invaluable. The varied response suggests that factors determining treatment success remained unknown. Likewise, most other trials have consisted of small uncontrolled patient series, with few randomized studies. Haemodialysis, diabetes mellitus and coronary arterial disease factors seemed to negatively affect angiogenesis. Severity of rest pain and number of repeated interventions, in particular bypass procedures, may negatively intervene with neo-capillary formation. SCT may eventually provide hope to patients and physicians. More research can help determine a specific group of patients that will benefit most.

Therapeutic Strategies of Stem Cell Transplantation for Liver Cirrhosis

Liver transplantation is widely regarded as the most effective therapy for end-stage liver diseases. However, stem cell-based therapy is being developed as a promising strategy which offers a number of benefits as it is minimally invasive and associated with low immunogenicity and low cost. This paper will review the major clinical issues surrounding the use of stem cell therapy for managing cirrhosis, such as discussing the selection of appropriate sub-types of bone marrow stem cells and the need for pre-differentiation into hepatocyte-like cells prior to transplantation, and providing an overview of the methods to improve cell viability and to prevent the exacerbation of cirrhosis. The role of human umbilical cord blood stem cells and amniotic epithelial cells for the treatment of liver disease will be also introduced.

Biomedical Applications of Gut Stem Cells: Gaining First-Hand Insights for Developing Therapy for the Future

Understanding developmental biology holds the key to the future of medicine as virtually every disease can be viewed as a failure of development. Broadly put, developmental biologists seek to understand the biology of stem cells to answer the immense complexity in the developmental process. If we can decipher the molecular cues important for the maintenance of stem cells it will boost our ability to understand how these cues may go awry in disease states and create effective therapeutics to fight against them. Moreover, in the era of personalized medicine cell therapy using stem cells hold greatest prospect of changing the face of human diseases and alleviating suffering in the near future. Use of stem cell therapy now hold a promising impact to treat various degenerative and genetic diseases including certain type of cancers, neurological diseases, autoimmune diseases, restoration of sight, wound healing, cardiac diseases, liver diseases, metabolic disorders, spinal cord injury and bone disorders etc. There are currently a number of stem cell sources that are being investigated for use in biomedical applications, including adult stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), wherein each presents its own unique advantages and disadvantages. Stem cells have the unique ability to continuously self-renew and differentiate into intermediate and mature cells of a variety of lineages. Though therapeutic potential of adult stem cells is the main focus of our research group; use of ESCs and iPSCs have also been regarded as promising candidates for future therapies considering their pluripotency and personalized therapeutic possibilities. Over the years gut stem cells has been used in analyzing adult stem cell behavior, identifying niche components, modelling pathogen-epithelia interactions, gene editing, disease modelling and orthotopic transplantation etc. The present review highlights the use of intestinal stem cells in various biomedical applications, and how it has helped us to understand many of the complex diseases including various genetic diseases, obesity and cancer and design effective therapy against them.

Huntington's disease: Molecular basis of pathology and status of current therapeutic approaches

Huntington's disease (HD) is a frequent and incurable hereditary neurodegenerative disorder that impairs motor and cognitive functions. Mutations in huntingtin (HTT) protein, which is essential for neuronal development, lead to the development of HD. An increase in the number of CAG repeats within the HTT gene, which lead to an expansion of polyglutamine tract in the resulting mutated HTT protein, which is toxic, is the causative factor of HD. Although the molecular basis of HD is known, there is no known cure for this disease other than symptomatic relief treatment approaches. The toxicity of mutHTT appears to be more detrimental to striatal medium spiny neurons, which degenerate in this disease. Therapeutic strategies addressing a reduction in the mutHTT content at the transcriptional level using zinc finger proteins and at the translational level with RNA interference and antisense oligonucleotides or promoting the proteosomal degradation of mutHTT are being studied extensively in preclinical models and also to a limited extent in clinical trials. The post-translational modification of mutHTT is another possibility that is currently being investigated for drug development. In addition to the pharmacological approaches, several lines of evidence suggested the potential therapeutic use of stem cell therapy, in particular using the patient-derived induced pluripotent stem cells, to replace the lost striatal neurons. The multi-pronged clinical investigations currently underway may identify therapies and potentially improve the quality of life for the HD patients in future.

Catechol-Functionalized Hyaluronic Acid Hydrogels Enhance Angiogenesis and Osteogenesis of Human Adipose-Derived Stem Cells in Critical Tissue Defects.

Over the last few decades, stem cell therapies have been highlighted for their potential to heal damaged tissue and aid in tissue reconstruction. However, materials used to deliver and support implanted cells often display limited efficacy, which has resulted in delaying translation of stem cell therapies into the clinic. In our previous work, we developed a mussel-inspired, catechol-functionalized hyaluronic acid (HA-CA) hydrogel that enabled effective cell transplantation due to its improved biocompatibility and strong tissue adhesiveness. The present study was performed to further expand the utility of HA-CA hydrogels for use in stem cell therapies to treat more clinically relevant tissue defect models. Specifically, we utilized HA-CA hydrogels to potentiate stem cell-mediated angiogenesis and osteogenesis in two tissue defect models: critical limb ischemia and critical-sized calvarial bone defect. HA-CA hydrogels were found to be less cytotoxic to human adipose-derived stem cells (hADSCs) in vitro compared to conventional photopolymerized HA hydrogels. HA-CA hydrogels also retained the angiogenic functionality of hADSCs and supported osteogenic differentiation of hADSCs. Because of their superior tissue adhesiveness, HA-CA hydrogels were able to mediate efficient engraftment of hADSCs into the defect regions. When compared to photopolymerized HA hydrogels, HA-CA hydrogels significantly enhanced hADSC-mediated therapeutic angiogenesis (promoted capillary/arteriole formation, improved vascular perfusion, attenuated ischemic muscle degeneration/fibrosis, and reduced limb amputation) and bone reconstruction (mineralized bone formation, enhanced osteogenic marker expression, and collagen deposition). This study proves the feasibility of using bioinspired HA-CA hydrogels as functional biomaterials for improved tissue regeneration in critical tissue defects.

Mesenchymal Stem Cells and Their Clinical Applications in Osteoarthritis.

Osteoarthritis is a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation. Chondrocytes in the matrix have a relatively slow turnover rate, and the tissue itself lacks a blood supply to support repair and remodeling. Researchers have evaluated the effectiveness of stem cell therapy and tissue engineering for treating osteoarthritis. All sources of stem cells, including embryonic, induced pluripotent, fetal, and adult stem cells, have potential use in stem cell therapy, which provides a permanent biological solution. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, and umbilical cord show considerable promise for use in cartilage repair. MSCs can be sourced from any or all joint tissues and can modulate the immune response. Additionally, MSCs can directly differentiate into chondrocytes under appropriate signal transduction. They also have immunosuppressive and anti-inflammatory paracrine effects. This article reviews the current clinical applications of MSCs and future directions of research in osteoarthritis.

Mesenchymal stem cell-based gene therapy for erectile dysfunction.

Despite the overwhelming success of PDE5 inhibitor (PDE5I), the demand for novel pharmacotherapeutic and surgical options for ED continues to rise owing to the increased proportion of elderly individuals in the population, in addition to the growing percentage of ED patients who do not respond to PDE5I. Surgical treatment of ED is associated with many complications, thus warranting the need for nonsurgical therapies. Moreover, none of the above-mentioned treatments essentially corrects, cures or prevents ED. Although gene therapy is a promising option, many challenges and obstacles such as local inflammatory response and random transgene expression, in addition to other safety issues, limit its use at the clinical level. The use of stem cell therapy alone also has many shortcomings. To overcome these inadequacies, many scientists and clinicians are investigating new gene and stem cell therapies.

Current status of treating neurodegenerative disease with induced pluripotent stem cells.

Degenerative diseases of the brain have proven challenging to treat, let alone cure. One of the treatment options is the use of stem cell therapy, which has been under investigation for several years. However, treatment with stem cells comes with a number of drawbacks, for instance the source of these cells. Currently, a number of options are tested to produce stem cells, although the main issues of quantity and ethics remain for most of them. Over recent years, the potential of induced pluripotent stem cells (iPSCs) has been widely investigated and these cells seem promising for production of numerous different tissues both in vitro and in vivo. One of the major advantages of iPSCs is that they can be made autologous and can provide a sufficient quantity of cells by culturing, making the use of other stem cell sources unnecessary. As the first descriptions of iPSC production with the transcription factors Sox2, Klf4, Oct4 and C-Myc, called the Yamanaka factors, a variety of methods has been developed to convert somatic cells from all germ layers to pluripotent stem cells. Improvement of these methods is necessary to increase the efficiency of reprogramming, the quality of pluripotency and the safety of these cells before use in human trials. This review focusses on the current accomplishments and remaining challenges in the production and use of iPSCs for treatment of neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease.

Dental and Nondental Stem Cell Based Regeneration of the Craniofacial Region: A Tissue Based Approach.

Craniofacial reconstruction may be a necessary treatment for those who have been affected by trauma, disease, or pathological developmental conditions. The use of stem cell therapy and tissue engineering shows massive potential as a future treatment modality. Currently in the literature, there is a wide variety of published experimental studies utilising the different stem cell types available and the plethora of available scaffold materials. This review investigates different stem cell sources and their unique characteristics to suggest an ideal cell source for regeneration of individual craniofacial tissues. At present, understanding and clinical applications of stem cell therapy remain in their infancy with numerous challenges to overcome. In spite of this, the field displays immense capacity and will no doubt be utilised in future clinical treatments of craniofacial regeneration.

Optimized Protocol is the Key for Clinical Use of Stem Cell Therapy in Stroke

Stroke is the second cause of mortality in industrial countries after ischemic heart disease. Ischemic stroke results from an artery occlusion and leads to oxygen and glucose shortage in brain. Cerebral ischemia results in inflammation and oxidative stress leading to neuronal loss and brain damage. To these days, rt-PA is the only approved drug for stroke; however, increasing the risk of bleeding and golden time limitation are the problems associated with rt-PA.

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart.

Adoptive transfer of multiple stem cell types has only had modest effects on the structure and function of failing human hearts. Despite increasing the use of stem cell therapies, consensus on the optimal stem cell type is not adequately defined. The modest cardiac repair and functional improvement in patients with cardiac disease warrants identification of a novel stem cell population that possesses properties that induce a more substantial improvement in patients with heart failure. To characterize and compare surface marker expression, proliferation, survival, migration, and differentiation capacity of cortical bone stem cells (CBSCs) relative to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs), which have already been tested in early stage clinical trials. CBSCs, MSCs, and CDCs were isolated from Gottingen miniswine or transgenic C57/BL6 mice expressing enhanced green fluorescent protein and were expanded in vitro. CBSCs possess a unique surface marker profile, including high expression of CD61 and integrin β4 versus CDCs and MSCs. In addition, CBSCs were morphologically distinct and showed enhanced proliferation capacity versus CDCs and MSCs. CBSCs had significantly better survival after exposure to an apoptotic stimuli when compared with MSCs. ATP and histamine induced a transient increase of intracellular Ca(2+) concentration in CBSCs versus CDCs and MSCs, which either respond to ATP or histamine only further documenting the differences between the 3 cell types. CBSCs are unique from CDCs and MSCs and possess enhanced proliferative, survival, and lineage commitment capacity that could account for the enhanced protective effects after cardiac injury.

An evaluation of the safety of adipose-derived stem cells

The adipose tissue contains a large numbers of stem cells; adipose-derived stem cells (ADSCs) can be em- ployed in regenerative medicine. This study was aimed at isolating ADSCs and evaluating the safety of ADSCs in mouse models. Stromal vascular fraction (SVF) was collected from the adipose tissue using collagenase. ADSCs were then isolated from SVFs by in vitro culture. The stemness of the ADSCs was evaluated in vitro based on their self-renewal potential, po- tential to differentiate into osteoblasts, and adipocytes, and the expression of specific markers. Finally, the tumor forma- tion ability of ADSCs was evaluated in vivo in athymic mice. Results showed that 100% of the ADSC samples developed well and maintained homogeneity up to passage 10. The ADSCs were completely sterilized and could not form tumors in athymic mice. These initial results showed that ADSCs were safe for use in stem cell therapy.