Trials Of Stem Cell Therapy Research Articles

A CASE REPORT: EXPLORING STARGARDT DISEASE - CLINICAL FEATURES AND GENETIC INSIGHTS

Stargardt disease (SD) stands as a prominent inherited macular dystrophy affecting both adults and children, characterized by bilateral and symmetrical maculopathy with autosomal recessive transmission linked to the ABCA4 gene. We aim to present a comprehensive exploration of SD, delving into its clinical manifestations, genetic intricacies, and potential therapeutic interventions. This case report highlights a 46-year-old north African male with late-onset STGD with gradual bilateral vision decline, central macular atrophy, and yellow deposits in the perimacular region. the spectrum of SD is diverse, ranging from childhood onset to adult manifestation, often mimicking age-related maculopathy. Stargardt diseases genetic landscape is intricately governed by the ABCA4 gene, marked by over 900 variants across its 50 exons. This genetic diversity extends to dominant genes such as STGD4, ELOVL4, and PRPH2, contributing to a spectrum of retinal disorders. Therapeutic approaches for Stargardt disease involve drugs targeting the visual cycle, a modified vitamin A, and ongoing gene replacement and stem cell therapy trials This comprehensive review amalgamates clinical observations, genetic considerations, and emerging therapeutic avenues.

Lung regeneration: diverse cell types and the therapeutic potential.

Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

Stem cell therapy: a new hope for stroke and traumatic brain injury recovery and the challenge for rural minorities in South Carolina.

Stroke and traumatic brain injury (TBI) are a significant cause of death and disability nationwide. Both are considered public health concerns in rural communities in the state of South Carolina (SC), particularly affecting the African American population resulting in considerable morbidity, mortality, and economic burden. Stem cell therapy (SCT) has emerged as a potential intervention for both diseases with increasing research trials showing promising results. In this perspective article, the authors aim to discuss the current research in the field of SCT, the results of early phase trials, and the utilization of outcome measures and biomarkers of recovery. We searched PubMed from inception to December 2023 for articles on stem cell therapy in stroke and traumatic brain injury and its impact on rural communities, particularly in SC. Early phase trials of SCT in Stroke and Traumatic Brain injury yield promising safety profile and efficacy results, but the findings have not yet been consistently replicated. Early trials using mesenchymal stem cells for stroke survivors showed safety, feasibility, and improved functional outcomes using broad and domain-specific outcome measures. Neuroimaging markers of recovery such as Functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) combined with neuromodulation, although not widely used in SCT research, could represent a breakthrough when evaluating brain injury and its functional consequences. This article highlights the role of SCT as a promising intervention while addressing the underlying social determinants of health that affect therapeutic outcomes in relation to rural communities such as SC. It also addresses the challenges ethical concerns of stem cell sourcing, the high cost of autologous cell therapies, and the technical difficulties in ensuring transplanted cell survival and strategies to overcome barriers to clinical trial enrollment such as the ethical concerns of stem cell sourcing, the high cost of autologous cell therapies, and the technical difficulties in ensuring transplanted cell survival and equitable healthcare.

Innovations in cell therapy in pediatric diseases: a narrative review.

Stem cell therapy is a regenerative medicine modality that has the potential to decrease morbidity and mortality by promoting tissue regeneration or modulating the inflammatory response. An increase in the number of clinical trials investigating the efficacy and safety of stem cell therapy in pediatric diseases has led to advancements in this field. Currently, multiple sources and types of stem cells have been utilized in the treatment of pediatric diseases. This review aims to inform researchers and clinicians about preclinical and clinical stem cell therapy trials in pediatric patients. We discuss the different types of stem cells and the wide spectrum of stem cell therapy trials for pediatric diseases, with an emphasis on the outcomes and advancements in the field. PubMed and clinicaltrials.gov databases were searched on October 28, 2022 using the following Medical Subject Headings (MeSH) terms "stem cell" or "stem cell therapy" with an age filter <18 years. Our search was limited to publications published between 2000 and 2022. Diverse sources of stem cells have different properties and mechanisms of action, which allow tailored application of stem cells according to the pathophysiology of the disease. Advancements in stem cell therapies for pediatric diseases have led to improvements in clinical outcomes in some pediatric diseases or in quality of life, such therapies represent a potential alternative to the current treatment modalities. Stem cell therapy in pediatric diseases has shown promising results and outcomes. However, further studies focusing on the implementation and optimal treatment timeframe are needed. An increase in preclinical and clinical trials of stem cell therapy targeting pediatric patients is required to advance our therapeutic applications.

Impact of caregivers' psychological and caregiving status on recruitment, conversion, and retention in stem cell therapy trials for cerebral palsy: A prospective survey analysis.

To examine specific correlates that may affect retention outcomes of neural stem cell therapy trials in families screened for cerebral palsy. A prospective correlational study. Primary caregivers completed surveys of psychological resilience, care burden and family caregiver tasks. The overall data and differences between groups were analysed and compared. Resilience was negatively correlated with the care ability and closely related to the monthly household income and educational level of the caregivers. Factors affecting the final retention rate included the type of disease, number of combined disorders, monthly household income, primary caregivers' education level and resilience. Economic level, literacy and psychological status may affect trial retention. These findings can provide tips for preparing for subsequent screening, identification and intervention in stem cell clinical trials. The study results may provide nursing care tips to make recruitment more efficient, reduce trial costs, support patient-centredness and accelerate trial progress. The target population involves the primary caregivers of children living with cerebral palsy. However, neither patients nor the public contributed to the design or conduct of the study, analysis, or interpretation of the data, or preparation of the manuscript.

Research progress in clinical trials of stem cell therapy for stroke and neurodegenerative diseases.

The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells are cells that can reproduce (self-renew) and differentiate into the body, which have shown significance in basic research, while doctors have also taken them into clinical trials to determine their efficacy and safety. Existing clinical trials mainly include middle-aged and elderly patients with stroke or Parkinson's disease (mostly 40-80 years old), mainly involving injection of mesenchymal stem cells and bone marrow mesenchymal stem cells through the veins and the putamen, with a dosage of mostly 106-108 cells. The neural and motor functions of the patients were restored after stem cell therapy, and the safety was found to be good during the follow-up period of 3 months to 5 years. Here, we review all clinical trials and the latest advances in stroke, Alzheimer's disease, and Parkinson's disease, with the hope that stem cell therapy will be used in the clinic in the future to achieve effective treatment rates and benefit patients.

Contemporary Challenges of Regenerative Therapy in Patients with Ischemic and Non-Ischemic Heart Failure.

It has now been almost 20 years since first clinical trials of stem cell therapy for heart repair were initiated. While initial preclinical data were promising and suggested that stem cells may be able to directly restore a diseased myocardium, this was never unequivocally confirmed in the clinical setting. Clinical trials of cell therapy did show the process to be feasible and safe. However, the clinical benefits of this treatment modality in patients with ischemic and non-ischemic heart failure have not been consistently confirmed. What is more, in the rapidly developing field of stem cell therapy in patients with heart failure, relevant questions regarding clinical trials' protocol streamlining, optimal patient selection, stem cell type and dose, and the mode of cell delivery remain largely unanswered. Recently, novel approaches to myocardial regeneration, including the use of pluripotent and allogeneic stem cells and cell-free therapeutic approaches, have been proposed. Thus, in this review, we aim to outline current knowledge and highlight contemporary challenges and dilemmas in clinical aspects of stem cell and regenerative therapy in patients with chronic ischemic and non-ischemic heart failure.

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retinal, cardiac, and dopamine-producing cells differentiated from human induced pluripotent stem (iPS) cells and hepatocyte-like cells differentiated from human embryonic stem (ES) cells. The distinctive feature of the stem cell research in Japan is the use of iPS cells. A national framework was also been set-up to attain the final goal: health insurance coverage. Now, insurance covers cell transplantation therapies for the repair and recovery of damaged skin, articular cartilage, and stroke as well as therapies introduced from abroad, such as allogeneic mesenchymal stem cells for graft-versus-host disease and chimeric antigen receptor-T (CAR-T) cell therapy. To prepare this review, original information was sought from Japanese authentic websites, which are reliable but a little hard to access due to the fact of multiple less-organized databases and the language barrier. Then, each fact was corroborated by citing its English version or publication in international journals as much as possible. This review provides a summary of progress over the past decade under the national program and a state-of-the-art factual view of research activities, government policy, and regulation in Japan for the realization of stem cell therapy.

Stem-Cell-Based Therapy: The Celestial Weapon against Neurological Disorders.

Stem cells are a versatile source for cell therapy. Their use is particularly significant for the treatment of neurological disorders for which no definitive conventional medical treatment is available. Neurological disorders are of diverse etiology and pathogenesis. Alzheimer's disease (AD) is caused by abnormal protein deposits, leading to progressive dementia. Parkinson's disease (PD) is due to the specific degeneration of the dopaminergic neurons causing motor and sensory impairment. Huntington's disease (HD) includes a transmittable gene mutation, and any treatment should involve gene modulation of the transplanted cells. Multiple sclerosis (MS) is an autoimmune disorder affecting multiple neurons sporadically but induces progressive neuronal dysfunction. Amyotrophic lateral sclerosis (ALS) impacts upper and lower motor neurons, leading to progressive muscle degeneration. This shows the need to try to tailor different types of cells to repair the specific defect characteristic of each disease. In recent years, several types of stem cells were used in different animal models, including transgenic animals of various neurologic disorders. Based on some of the successful animal studies, some clinical trials were designed and approved. Some studies were successful, others were terminated and, still, a few are ongoing. In this manuscript, we aim to review the current information on both the experimental and clinical trials of stem cell therapy in neurological disorders of various disease mechanisms. The different types of cells used, their mode of transplantation and the molecular and physiologic effects are discussed. Recommendations for future use and hopes are highlighted.

Stem Cell-based Therapeutic and Diagnostic Approaches in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative impairment mainly recognized by memory loss and cognitive deficits. However, the current therapies against AD are mostly limited to palliative medications, prompting researchers to investigate more efficient therapeutic approaches for AD, such as stem cell therapy. Recent evidence has proposed that extensive neuronal and synaptic loss and altered adult neurogenesis, which is perceived pivotal in terms of plasticity and network maintenance, occurs early in the course of AD, which exacerbates neuronal vulnerability to AD. Thus, regeneration and replenishing the depleted neuronal networks by strengthening the endogenous repair mechanisms or exogenous stem cells and their cargoes is a rational therapeutic approach. Currently, several stem cell-based therapies as well as stem cell products like exosomes, have shown promising results in the early diagnosis of AD. This review begins with a comparison between AD and normal aging pathophysiology and a discussion on open questions in the field. Next, summarizing the current stem cell-based therapeutic and diagnostic approaches, we declare the advantages and disadvantages of each method. Also, we comprehensively evaluate the human clinical trials of stem cell therapies for AD. Peer-reviewed reports were extracted through Embase, PubMed, and Google Scholar until 2021. With several ongoing clinical trials, stem cells and their derivatives (e.g., exosomes) are an emerging and encouraging field in diagnosing and treating neurodegenerative diseases. Although stem cell therapies have been successful in animal models, numerous clinical trials in AD patients have yielded unpromising results, which we will further discuss.

Cross-Sectional Survey of Clinical Trials of Stem Cell Therapy for Heart Disease Registered at ClinicalTrials.gov.

Objective: It is important to register clinical trials before their implementation. There is a lack of study to evaluate registered clinical trials of stem cell therapy for heart diseases. Our study used the registration information at ClinicalTrials.gov to provide an overview of the registered trials investigating stem cell therapy for heart diseases.Methods: We searched ClinicalTrials.gov from inception to October 1, 2020 to identify clinical trials evaluating stem cell therapy for heart diseases. These trials were included in a cross-sectional survey and descriptive analysis. The outcomes included start date, completion date, location, status, study results, funding, phase, study design, conditions, interventions, sex, age, and sample size of those trials, as well as conditions, efficacy, safety and samples of the publications. SPSS 24.0 software was used for the statistical analysis.Results: A total of 241 trials were included. The registration applications for most trials originated from the United States, and the research start date ranged from 2001 to 2025. More than half of the trials have been completed, but few trials have published results (15.62%). The funding source for 81.12% of trials was recorded as “other” because the specific funding source was not indicated. There were 226 (93.78%) interventional studies and 15 (6.22%) observational studies; among all 241 studies, only 2.90% were phase 4 trials. Most interventional studies used randomized allocation, parallel assignment, and blinding. Of the observational studies, 6 were cohort studies (40.00%) and 73.33% were prospective. The most common disease was coronary artery disease (57.68%) and 98.34% included both male and female participants. The sample size included fewer than 50 patients in 58.51% of trials, and only 18 trials (7.47%) lasted more than 121 months. The registered details were illogical for nine trials (3.8%) that included 0 subjects and two trials (0.8%) that had a duration of 0 months (0.8%). In term of publications of the trials, most of the publications of the trials showed efficacy and safety in stem cell therapy for heart disease.Conclusion: The clinical trials investigating stem cell therapy for heart diseases registered at ClinicalTrials.gov are mostly interventional studies, and only a few are phase 4 trials. Most trials have a small sample size, and few have a duration of more than 121 months. Most of the completed trials did not publish their results, and some of the registration information was incomplete and illogical.

Prospects for Stem Cell-Based Regenerative Therapies in India

Stem cells offer a promising therapeutic strategy to not only treat several incurable diseases but also regenerate damaged tissues. The current global boom in the field of stem cell and regenerative therapies had led to India becoming a global hotspot for stem cell-based therapies. In this review, we assess the current status of stem cell therapy trials in India and show that the bone marrow-derived stem cells, like mesenchymal stem/stromal cells (MSCs), are predominantly used. Phase 1 and 2 clinical trials have also used MSCs to alleviate symptoms of severe novel coronavirus infections. Recent breakthroughs in gene editing technologies, combined with stem cell therapy, can be effectively harnessed to devise large-scale and affordable treatments for haematological diseases that are highly prevalent in India, like beta-thalassemia and sickle cell diseases. Innovations in stem cell therapy in India can make treatments more affordable to address the needs of in-country patients.

Stem cell therapy in children with acute liver failure: The dream could come true

Acute liver failure (ALF) in children is a severe disease with a high mortality rate. The current treatment strategies are still defective, with many cases die when liver transplantation is unavailable. The current protocol of steroids therapy improved the survival rate of hepatitis A virus (HAV)-related ALF. However, there is still a high mortality for non-HAV cases. Stem cell therapy (SCT) has been tried in experimental animals with ALF and in few adult studies with acute-on-chronic liver failure. No previous trials of SCT have been tested in children with ALF. The absence of SCT application in ALF in children could be due to some issues. These could be related to safety, sources, administration route, optimum dosage, efficacy, and survival. It is proposed that could be the future therapy if these obstacles have been well studied and solved.

Stem Cell Therapy in Single-Ventricle Physiology: Recent Progress and Future Directions.

Current surgical and medical treatment options for single ventricle physiology conditions remain palliative. On the long term, despite treatment, the systemic ventricle has a significant risk of developing failure. There are unmet needs to develop novel treatment modalities to help ameliorate the ventricular dysfunction. Advances in the field of stem cell therapy have been promising for the treatment of heart failure. Numerous stem cell populations have been identified. Preclinical studies in small and large animal models provide evidence for effectiveness of this treatment modality and reveal several mechanisms of action by which stem cells exert their effect. Many clinical trials have been designed to further investigate the therapeutic potential that stem cell therapy may hold for pediatric populations with single ventricle physiology. In this review, we discuss the stem cell types used in these populations, some preclinical studies, and the clinical trials of stem cell therapy in single ventricle patients.

Neuroprotectors in hypoxic ischemic encephalopathy in neonates: a systematic review

Objective The aim was to discuss the neuroprotectors in hypoxic ischemic encephalopathy (HIE) in neonates.Materials and methodsA systematic review of MEDLINE (PubMed, Medscape, Science Direct, and EMF-Portal) and internet was conducted on all articles published from 2002 to 2018. English-language reports of the neuroprotectors in HIE in neonates were searched. The initial search presented 117 articles, where 29 had inclusion criteria. Articles not reporting on the neuroprotectors in HIE in the title or abstract were not included. A total of five independent investigators extracted data on methods. Comparisons were made by a structured review, with the results tabulated. A total of seven studies were about hypoxic ischemic encephalopathy in neonates, nine about experimental translational studies, and 13 about current clinical trial studies for neuroprotectors in HIE.Results HIE is still a serious condition that is unresolved and causes significant mortality and long-term morbidity. Approximately 20–25% of term newborn infants die during the neonatal period and ∼25% of those who survive develop permanent neurological disabilities. Several studies showed that there were neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-β, and stem cell transplantation. Owing to the lack of imaging diagnostic difficulties to detect HIE in premature newborns and insufficient data, present stem cell therapy trials are restricted to full-term infants. Besides stem cell transplantation, there is research ongoing in the field of stem cell factors.ConclusionSome gaps in the knowledge concerning the pathophysiology and the timing of important endogenous neuroprotective and neuroregenerative mechanisms still exist. To make basic science results more clinically relevant and translational, combinational therapies with hypothermia should be considered and studied. There is also a need for more biomarker studies that can be used along with the brain imaging, and long-term neuroassessments.

Autologous Bone-Marrow vs. Peripheral Blood Mononuclear Cells Therapy for Peripheral Artery Disease in Diabetic Patients.

Diabetes mellitus (DM) remains one of the most important risk factors for peripheral artery disease (PAD), with approximately 20% of DM patients older than 40 years old are affected with PAD. The current standard management for severe PAD is endovascular intervention with or without surgical bypass. Unfortunately, up to 40% of patients are unable to undergo these revascularization therapies due to excessive surgical risk or adverse vascular side effects. Stem cell therapy has emerged as a novel therapeutic strategy for these ‘no-option’ patients. Several types of stem cells are utilized for PAD therapy, including bone marrow mononuclear cells (BMMNC) and peripheral blood mononuclear cells (PBMNC). Many studies have reported the safety of BMMNC and PBMNC, as well as its efficacy in reducing ischemic pain, ulcer size, pain-free walking distance, ankle-brachial index (ABI), and transcutaneous oxygen pressure (TcPO2). However, the capacity to establish the efficacy of reducing major amputation rates, amputation free survival, and all-cause mortality is limited, as shown by several randomized placebo-controlled trials. The present literature review will focus on comparing safety and efficacy between BMMNC and PBMNC as cell-based management in diabetic patients with PAD who are not suitable for revascularization therapy.

Progress in clinical trials of stem cell therapy for cerebral palsy.

Cerebral palsy is the most common disease in children associated with lifelong disability in many countries. Clinical research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral palsy. Stem cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem cells. In this review, we summarize the design schemes and results of these clinical trials. Our findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical trials. Furthermore, we also assess the safety and efficacy of these clinical trials. We anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.

Diffusion tensor imaging of the spinal cord status post trauma.

Background: Since its development in 1994, diffusion tensor imaging (DTI) has been successfully used to assess structural and functional changes to neurological tissue within the central nervous system. Namely, DTI is a noninvasive magnetic resonance imaging (MRI)-based technique that uses anisotropic diffusion to visualize and estimate the organization of white matter in neuronal tissue. It has been used to study various spinal pathologies including neoplastic diseases, degenerative myelopathy, demyelinating diseases, and infections involving the spinal cord. However, due to technical uncertainties and experimental limitations, DTI has rarely been clinically applied to assess trauma-related spinal pathologies.Methods: An extensive review of the published literature on DTI was performed utilizing PubMed, OVID Medline, and EMBASE journals. Terms used for the search included DTI and spine trauma.Results: The search yielded full text English language-related articles regarding DTIs application, limitations, and functional outcomes secondary to spinal trauma.Conclusion: DTI relies on anisotropy in CNS tissues to determine the spatial orientation of surrounding axon tracts and define anatomical boundaries. Diffusion along three principle axes is used to calculate the following four DTI indices; fractional anisotropy, apparent diffusion coefficient (ADC), longitudinal ADC, and transverse ADC. Using DTI as a diagnostic tool status, post spine trauma has proven useful in examining the morphological and physiological extent of spinal lesions beyond conventional MRI. Experimental studies are now utilizing DTI to analyze the severity of spinal cord trauma during the hyperacute phase and may potentially be used to providing additional diagnostic information for improved treatment efficiency (e.g., as shown during the stem cell therapy trials).

Safety and Efficacy of Stem Cell Therapy in Patients With Ischemic Stroke.

Stem cell therapy is emerging as a promising treatment strategy to treat patients with stroke. While there are established modes of treatment for stroke patients such as thrombolysis and endovascular intervention, most of the stroke patients frequently end up with major residual deficits or even death. The use of stem cells to treat stroke has been found to be beneficial in the animal models but strict evidence for the same in humans is still lacking. We reviewed 13 clinical trials of stem cell therapy in stroke patients conducted between 2014 and 2020 based on the search using the database PubMed, and the clinical trial registry (www.clinicaltrials.gov). We aimed to assess the safety and efficacy of stem cell treatment in stroke patients who participated in the trials. Quality assessment of the clinical trials revealed a sub-optimal score. We found mixed results regarding the efficacy of stem cells in the treatment of ischemic stroke although we could not do a quantitative analysis of the effect outcomes. Assessment for safety revealed promising results as there were only minor side effects related to cell therapy. Although stem cell therapy seems to be a promising strategy to treat stroke patients in the future, we concluded that the field needs more evidence regarding the safety and efficacy of the use of stem cells in stroke patients before we use them in the clinic.