Advantages and challenges of stem cell therapy for osteoarthritis (Review).
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ABSTRACT:
SUBMITTER: Loo SJQ
PROVIDER: S-EPMC8212446 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Autoimmune liver disease (AILD) is a series of chronic liver diseases with abnormal immune responses, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The treatment options for AILD remain limited, and the adverse side effects of the drugs that are typically used for treatment frequently lead to a low quality of life for AILD patients. Moreover, AILD patients may have a poor prognosis, especially those with an incomplete response to first-line treatment. Mesenchymal stem cells (MSCs) are pluripotent stem cells with low immunogenicity and can be conveniently harvested. MSC-based therapy is emerging as a promising approach for treating liver diseases based on their advantageous characteristics of immunomodulation, anti-fibrosis effects, and differentiation to hepatocytes, and accumulating evidence has revealed the positive effects of MSC therapy in AILD. In this review, we first summarize the mechanisms, safety, and efficacy of MSC treatment for AILD based on work in animal and clinical studies. We also discuss the challenges of MSC therapy in clinical applications. In summary, although promising data from preclinical studies are now available, MSC therapy is currently far for being applied in clinical practice, thus developing MSC therapy in AILD is still challenging and warrants further research.
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Project description:Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.
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Project description:Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.
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Project description:Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.
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Project description:Since its eruption in China, novel coronavirus disease (COVID-19) has been reported in most of the countries and territories (>200) of the world with ∼18 million confirmed cases (as of August 3, 2020). In most of the countries, COVID-19 upsurge is uncontrolled with a significant mortality rate. Currently, no treatment effective for COVID-19 is available in the form of vaccines or antiviral drugs and patients are currently treated symptomatically. Although the majority of the patients develop mild symptoms and recover without mechanical ventilation for respiratory management, severe respiratory illness develops in a significant portion of affected patients and may result in death. While the scientific community is working to develop vaccines and drugs against the COVID-19 pandemic, novel alternative therapies may reduce the mortality rate. Recent use of stem cells for critically ill COVID-19 patients in a small group of patients in China and subsequent Emergency Use Authorization of stem cells by Food and Drug Administration to Global Institute of Stem Cell Therapy and Research and Athersys has created excitement among the medical community. As a result, several clinical trials have been registered using stem cells for COVID-19 treatment that aim to use different cell sources, dosage, and importantly diverse targeted patient groups. In this brief review, the possibilities of stem cell use in COVID-19 patients and relevant challenges in their use have been discussed.
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Project description:Background and objectiveStem cell therapy (SCT) is one of the vastly researched branches of regenerative medicine as a therapeutic tool to treat incurable diseases. With the use of human stem cells such as embryonic stem cells (ESCs), adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs), stem cell therapy aims to regenerate or repair damaged tissues and congenital defects. As stem cells are able to undergo infinite self-renewal, differentiate into various types of cells and secrete protective paracrine factors, many researchers have investigated the potential of SCT in regenerative medicine. Therefore, this review aims to provide a comprehensive review on the recent application of SCT in various intractable diseases, namely, haematological diseases, neurological diseases, diabetes mellitus, retinal degenerative disorders and COVID-19 infections along with the challenges faced in the clinical translation of SCT.MethodsAn extensive search was conducted on Google scholar, PubMed and Clinicaltrials.gov using related keywords. Latest articles on stem cell therapy application in selected diseases along with their challenges in clinical applications were selected.Key content and findingsIn vitro and in vivo studies involving SCT are shown to be safe and efficacious in treating various diseases covered in this review. There are also a number of small-scale clinical trials that validated the positive therapeutic outcomes of SCT. Nevertheless, the effectiveness of SCT are highly variable as some SCT works best in patients with early-stage diseases while in other diseases, SCT is more likely to work in patients in late stages of illnesses. Among the challenges identified in SCT translation are uncertainty in the underlying stem cell mechanism, ethical issues, genetic instability and immune rejection.ConclusionsSCT will be a revolutionary treatment in the future that will provide hope to patients with intractable diseases. Therefore, studies ought to be done to ascertain the long-term effects of SCT while addressing the challenges faced in validating SCT for clinical use. Moreover, as there are many studies investigating the safety and efficacy of SCT, future studies should look into elucidating the regenerative and reparative capabilities of stem cells which largely remains unknown.
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Project description:The coronavirus disease 2019 (COVID-19) global pandemic continues and antiviral agents and vaccines are currently under investigation. Mesenchymal stem cell (MSC)-based therapy can be a suitable option for management of patients with COVID-19 at the urgent time of virus outbreak. Currently, MSCs are being explored against the novel infectious disease due to their therapeutic properties of anti-inflammation, immunomodulation and tissue repair and regeneration, albeit the precise mechanisms of MSC action toward COVID-19 remain unclear. To date, rigorous results from clinical trials using MSCs in human have been weakly positive. The pervasive uncertainty of using MSC therapeutic products as an effective combatant against COVID-19 requires rigorous resolution on several fronts, including MSC fate after infusion, safety issue, homing capability, and MSC resistance to the disease microenvironment. Focusing on these facets, a few important ones will be critically analyzed and addressed in this article for the development of safe and effective MSC-based therapies for COVID-19.
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Project description:Kidney disease (KD) is a life-threatening disease characterized by high morbidity and mortality in clinical settings, which can be caused by many reasons, and the incidence increases with age. However, supportive therapy and kidney transplantation still have limitations in alleviating KD progression. Recently, mesenchymal stem cells (MSCs) have shown great potential in repairing injury through their multidirectional differentiation and self-renewal ability. Of note, MSCs serve as a safe and effective therapeutic strategy for treating KD in preclinical and clinical trials. Functionally, MSCs ameliorate KD progression by regulating the immune response, renal tubular cell apoptosis, tubular epithelial-mesenchymal transition, oxidative stress, angiogenesis, and so on. In addition, MSCs exhibit remarkable efficacy in both acute kidney injury (AKI) and chronic kidney disease (CKD) through paracrine mechanisms. In this review, we outline the biological characteristics of MSCs, discuss the efficacy and mechanisms of MSCs-based therapy for KD, summarize the completed and ongoing clinical trials, as well as analyze limitations and new strategies, aiming to provide new ideas and approaches for the preclinical experiments and clinical trials of MSCs transplantation for KD.
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