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Cell Stem Cell Oct 2020Human pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provide unprecedented opportunities for cell therapies... (Review)
Review
Human pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provide unprecedented opportunities for cell therapies against intractable diseases and injuries. Both ESCs and iPSCs are already being used in clinical trials. However, we continue to encounter practical issues that limit their use, including their inherent properties of tumorigenicity, immunogenicity, and heterogeneity. Here, I review two decades of research aimed at overcoming these three difficulties.
Topics: Cell- and Tissue-Based Therapy; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 33007237
DOI: 10.1016/j.stem.2020.09.014 -
Stem Cell Research & Therapy Feb 2019In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great... (Review)
Review
In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Graphite; Humans; Induced Pluripotent Stem Cells; Stem Cell Transplantation; Stem Cells; Tissue Scaffolds
PubMed: 30808416
DOI: 10.1186/s13287-019-1165-5 -
South African Medical Journal =... Sep 2019Neurological disease encompasses a diverse group of disorders of the central and peripheral nervous systems, which collectively are the leading cause of disease burden... (Review)
Review
Neurological disease encompasses a diverse group of disorders of the central and peripheral nervous systems, which collectively are the leading cause of disease burden globally. The scope of treatment options for neurological disease is limited, and drug approval rates for improved treatments remain poor when compared with other therapeutic areas. Stem cell therapy provides hope for many patients, but should be tempered with the realisation that the scientific and medical communities are still to fully unravel the complexities of stem cell biology, and to provide satisfactory data that support the rational, evidence-based application of these cells from a therapeutic perspective. We provide an overview of the application of stem cells in neurological disease, starting with basic principles, and extending these to describe the clinical trial landscape and progress made over the last decade. Many forms of stem cell therapy exist, including the use of neural, haematopoietic and mesenchymal stem cells. Cell therapies derived from differentiated embryonic stem cells and induced pluripotent stem cells are also starting to feature prominently. Over 200 clinical studies applying various stem cell approaches to treat neurological disease have been registered to date (Clinicaltrials.gov), the majority of which are for multiple sclerosis, stroke and spinal cord injuries. In total, we identified 17 neurological indications in clinical stage development. Few studies have progressed into large, pivotal investigations with randomised clinical trial designs. Results from such studies will be essential for approval and application as mainstream treatments in the future.
Topics: Cell- and Tissue-Based Therapy; Humans; Nervous System Diseases; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Stem Cells
PubMed: 31662153
DOI: 10.7196/SAMJ.2019.v109i8b.14009 -
Biology of Blood and Marrow... Apr 2019Chimeric antigen receptor (CAR)-modified T cells (CAR-Ts) targeting CD19 have resulted in unprecedented durable remissions for patients with relapsed and refractory B... (Review)
Review
Chimeric antigen receptor (CAR)-modified T cells (CAR-Ts) targeting CD19 have resulted in unprecedented durable remissions for patients with relapsed and refractory B cell malignancies. Cytokine release syndrome (CRS), resulting from rapid immune activation induced by CAR-Ts, is the most significant treatment-related toxicity. CRS initially manifests with fever and can progress to life-threatening capillary leak with hypoxia and hypotension. The clinical signs of CRS correlate with T cell activation and high levels of cytokines including IL-6. Tocilizumab, an anti-IL-6 receptor antagonist, is the standard for CRS management, but optimal timing of administration is unclear. The development of a supportive infrastructure by treatment centers is important to maintain safe administration as access expands. Collaborative efforts are underway to harmonize the definition and grading of CRS to allow for better interpretation of toxicities across CAR-T products and clinical trials and allow for informed management algorithms.
Topics: Cell- and Tissue-Based Therapy; Cytokine Release Syndrome; Humans; Receptors, Chimeric Antigen
PubMed: 30586620
DOI: 10.1016/j.bbmt.2018.12.756 -
Rinsho Shinkeigaku = Clinical Neurology Mar 2019Cell therapy for Parkinson's disease has a history of being applied clinically with aborted embryos as donor source. Efficacy of the therapy under the appropriate... (Review)
Review
Cell therapy for Parkinson's disease has a history of being applied clinically with aborted embryos as donor source. Efficacy of the therapy under the appropriate condition has been reported. Based on this experience and the advancement of stem cell technology, clinical trials of cell therapy with embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) are going to start soon in several countries. In Japan a physician-initiated clinical trial of iPSC-based therapy for Parkinson's disease has launched since 2018. This trial adopts allogeneic transplantation with a cell line from iPSC stock. This article discusses patient selection, procedure, and risk of the therapy. It also introduces the world's current situation of the cell therapy for Parkinson's disease.
Topics: Animals; Autografts; Carcinogenesis; Cell- and Tissue-Based Therapy; Dopaminergic Neurons; Dyskinesias; Embryonic Stem Cells; HLA Antigens; Histocompatibility; Humans; Immune Tolerance; Induced Pluripotent Stem Cells; Parkinson Disease; Risk; Stem Cell Transplantation
PubMed: 30814448
DOI: 10.5692/clinicalneurol.cn-001235 -
Frontiers in Immunology 2020Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR),... (Review)
Review
Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR), and ACT has made a great difference in treating multiple types of tumors. ACT is not perfect, and it can be followed by severe side effects, which hampers the application of ACT in clinical trials. One of the most promising methods to minimize side effects is to endow adoptive T cells with the ability to target neoantigens, which are specific to tumor cells. With the development of antigen screening technologies, more methods can be applied to discover neoantigens in cancer cells, such as whole-exome sequencing combined with mass spectrometry, neoantigen screening through an inventory-shared neoantigen peptide library, and neoantigen discovery via trogocytosis. In this review, we focus on the side effects of existing antigens and their solutions, illustrate the strategies of finding neoantigens in CAR-T and TCR-T therapies through methods reported by other researchers, and summarize the clinical behavior of these neoantigens.
Topics: Animals; Antigens, Neoplasm; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Mass Spectrometry; Mice; Neoplasms; Receptors, Chimeric Antigen; Exome Sequencing
PubMed: 32194541
DOI: 10.3389/fimmu.2020.00176 -
CNS Neuroscience & Therapeutics Jun 2020
Topics: Brain Injuries, Traumatic; Cell- and Tissue-Based Therapy; Humans; Regenerative Medicine
PubMed: 32452140
DOI: 10.1111/cns.13397 -
Cell Stem Cell Oct 2021An exceptional safety profile has been shown in a large number of cell therapy clinical trials that use mesenchymal stromal cells (MSCs). However, reliable potency... (Review)
Review
An exceptional safety profile has been shown in a large number of cell therapy clinical trials that use mesenchymal stromal cells (MSCs). However, reliable potency assays are still lacking to predict MSC immunosuppressive efficacy in the clinical setting. Nevertheless, MSCs are approved in Japan and Europe for the treatment of graft-versus-host and Crohn's fistular diseases, but not in the United States for any clinical indication. We discuss potential mechanisms of action for the therapeutic effects of MSC transplantation, experimental models that dissect tissue modulating function of MSCs, and approaches for identifying MSC effects in vivo by integrating biomarkers of disease and MSC activity.
Topics: Biomarkers; Cell- and Tissue-Based Therapy; Graft vs Host Disease; Humans; Japan; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 34624232
DOI: 10.1016/j.stem.2021.09.006 -
Current Problems in Surgery Jul 2014The efficacy of NPWT in promoting wound healing has been largely accepted by clinicians, yet the number of high-level clinical studies demonstrating its effectiveness is... (Review)
Review
The efficacy of NPWT in promoting wound healing has been largely accepted by clinicians, yet the number of high-level clinical studies demonstrating its effectiveness is small and much more can be learned about the mechanisms of action. In the future, hopefully we will have the data to assist clinicians in selecting optimal parameters for specific wounds including interface material, waveform of suction application, and the amount of suction to be applied. Further investigation into specific interface coatings and instillation therapy are also needed. We believe that advances in mechanobiology, the science of wound healing, the understanding of biofilms, and advances in cell therapy will lead to better care for our patients.
Topics: Bandages; Biofilms; Cell- and Tissue-Based Therapy; Female; Humans; Male; Negative-Pressure Wound Therapy; Occlusive Dressings; Suction; Treatment Outcome; Wound Healing; Wounds and Injuries
PubMed: 24935079
DOI: 10.1067/j.cpsurg.2014.04.001 -
Molecular Therapy : the Journal of the... Mar 2020
Topics: Cell- and Tissue-Based Therapy; Genetic Therapy; Humans; Immunity
PubMed: 32023479
DOI: 10.1016/j.ymthe.2020.01.024