Stem Cell-Based Cell Therapy in Neurological Diseases: A Review

ArticleinJournal of Neuroscience Research 87(10):2183-200 · August 2009with40 Reads
DOI: 10.1002/jnr.22054 · Source: PubMed
Human neurological disorders such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, multiple sclerosis (MS), stroke, and spinal cord injury are caused by a loss of neurons and glial cells in the brain or spinal cord. Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. In recent years, neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells, mesenchymal stem cells, and neural stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We review here notable experimental and preclinical studies previously published involving stem cell-based cell and gene therapies for Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, MS, stroke, spinal cord injury, brain tumor, and lysosomal storage diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. There are still many obstacles to be overcome before clinical application of cell therapy in neurological disease patients is adopted: 1) it is still uncertain what kind of stem cells would be an ideal source for cellular grafts, and 2) the mechanism by which transplantation of stem cells leads to an enhanced functional recovery and structural reorganization must to be better understood. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell-based cell therapies for neurological diseases.
    • We treated 15 ALS patients by injecting IT stem cells aimed to improve MN function. Human intrathecal transplantation of peripheral blood stem cells have been previously attempted in patients with ALS[25]as well as BM derived stem cells in other neurological disorders like cerebral palsy, stroke, autism and spinal cord injury, with promising results and no relevant complications[8,18,23,30,31]. Although Janson in 2001 described IT transplantation of human stem cells obtained from peripheral blood 25 to our knowledge this is the first study that includes IT G-CSF stimulated BM cells for the treatment of patients suffering from ALS, and the more important goal of this study was to clarify the safety of IT administration of BM cells without the use of apheresis, selection, or ex-vivo cell-expansion methods, using a simplified and affordable procedure in an ambulatory setting.
    Full-text · Article · Jan 2017 · European Journal of Medicinal Chemistry
    • Therapeutic strategy using stem or progenitor cells was proposed as a possibility to treat neurodegenerative disorders replacing the injured brain tissues with cell implants. Embryonic stem cells, mesenchymal stem cells, and neural stem or progenitor cells were proposed as cell candidates [4][5][6][7]. Among these cells, neural stem or progenitor cells were found promising as they are able to differentiate to neurons if implanted [8][9][10][11].
    [Show abstract] [Hide abstract] ABSTRACT: Background: Facilitation of the differentiation of the stem cells toward neuronal lineage is crucial for enhancing the differentiation efficacy of grafted stem cells for the possible treatment of neurodegenerative disorders. MicroRNA124a (miR-124a) has been considered as a neuronal lineage regulator, possessing the capability to activate neuronal differentiation. In this study, using a neuronal promoter-based reporter and live-cell fluorescence imaging, we visualized in vitro and in vivo the enhanced neuronal differentiation of neuronal progenitor cells with miR-124a overproduction. Methods: The neuron specific alpha1 tubulin promoter-driven RFP reporter (pTa1-RFP) was used to trace the miR-124a-induced neuronal differentiation in live cell condition. MiR-124a or miR-scramble in 10 % glucose buffer was mixed with in vivo-jetPEITM and in vivo fluorescence images were obtained daily using Maestro spectral fluorescent imager. Results: Neurite outgrowth was clearly seen in F11 cells after miR-124a transfection, and immunofluorescence staining showed increase of Tuj1 and NF at 48 hours. When pTa1-RFP-transfected F11 cells were implanted simultaneously with miR-124a into the nude mice, gradually increasing reporter signals and morphological changes indicated neuronal differentiation for 48 hours in live cells in vitro. The miR-124a-treated F11 cells showed higher reporter signals on in vivo fluorescence imaging than miR-scramble-treated cells, which were verified by ex vivo confirmation of Tuj1 and NF expression. Conclusions: These results indicated that neuronal reporter-based neurogenesis imaging can be used for monitoring miR-124a acting as neuronal activator when miRNA was injected in in vivo PEI-coated form for miRNA-mediated regenerative therapy.
    Full-text · Article · Dec 2016
    • Especially stem cell therapy has great potential to cure many injuries and diseases. Stem cells have the ability to continuously divide and differentiate into various kinds of cells or tissues [1]. The main types of stem cells are embryonic stem cell (ESC), adult stem cell (ASC), and induced pluripotent stem cell (iPSC).
    [Show abstract] [Hide abstract] ABSTRACT: Direct reprogramming which changes the fate of matured cell is a very useful technique with a great interest recently. This approach can eliminate the drawbacks of direct usage of stem cells and allow the patient specific treatment in regenerative medicine. Overexpression of diverse factors such as general reprogramming factors or lineage specific transcription factors can change the fate of already differentiated cells. On the other hand, biomaterials can provide physical and topographical cues or biochemical cues on cells, which can dictate or significantly affect the differentiation of stem cells. The role of biomaterials on direct reprogramming has not been elucidated much, but will be potentially significant to improve the efficiency or specificity of direct reprogramming. In this review, the strategies for general direct reprogramming and biomaterials-guided stem cell differentiation are summarized with the addition of the up-to-date progress on biomaterials for direct reprogramming.
    Full-text · Article · Dec 2016
    • Cell-based therapy and gene transfer to the diseased brain have been provided to explore the possibility of developing new powerful therapeutic methods for a spectrum of human neurological disorders. Indeed, the lack of appropriate cell types for cell therapy in patients with the neurological disorders has caused the development of this therapeutic procedure[17]. The main sources of stem cells for neurotherapy include ESCs, stem cells from the fetal or adult central nervous system, or other tissues such as bone marrow and cord blood (Fig. 1)[18][19][20].
    [Show abstract] [Hide abstract] ABSTRACT: Cerebral palsy (CP) is a neuromuscular disease due to injury in the infant’s brain. The CP disorder causes many neurologic dysfunctions in the patient. Various treatment methods have been used for the management of CP disorder. However, there has been no absolute cure for this condition. Furthermore, some of the procedures which are currently used for relief of symptoms in CP, cause discomfort or side effects in the patient. Recently, stem cell therapy has attracted a huge interest as a new therapeutic method for treatment of CP. Several investigations in animal and human with CP have been demonstrated positive potential of stem cell transplantation for the treatment of CP disorder. The ultimate goal of this therapeutic method is to harness the regenerative capacity of the stem cells causing a formation of new tissues to replace the damaged tissue. During the recent years, there have been many investigations on stem cell therapy. However, there are still many unclear issues regarding this method and high effort is needed to create a technology as a perfect treatment. This review will discuss the scientific background of stem cell therapy for cerebral palsy including evidences from current clinical trials.
    Full-text · Article · Aug 2016
    • The results of stem cell therapies in neuronal replacement and regeneration has brought a ray of hope and immense expectation for ALS patients [168] . Many preclinical works have been done by transplanting different types of cells like embryonic stem cells (ESCs), neural stem cells (NSCs), bone marrow cells, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) [169][170][171][172]in mouse models of ALS (Table 2). The availability of induced pluripotent stem cells (iPSCs), which can be differentiated into specific neural populations, open an exciting field for neurological research and drug development.
    [Show abstract] [Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, associated with motor neuron degeneration, muscle weakness, paralysis and finally death. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and proteasomal dysfunction. Although numerous pathological mechanisms have been explained, ALS remains incurable disease because of failure of clinical trials and lack of any effective therapy. The rapid advancement in genetic discoveries in ALS emphasizes the point that ALS is a multi-subtype syndrome rather than a single disease. This can be argued as one of the single reason why many previous therapeutic drug trials have failed. Efforts to develop novel ALS treatments which target specific pathomechanisms are currently being pursued. Herein, we review the recent discovery and preclinical characterization of neuroprotective compounds and compare their effects on disease onset, duration and survival. Furthermore, the structure-activity relationships of these agents are analyzed with the overall goal of developing a screening strategy for future clinical applications.
    Full-text · Article · Jun 2016
    • Efficient and targeted delivery of antigens, immunomodulatory or immunostimulatory molecule to the appropriate cell is critical for an efficient immunotherapy . Stem-cell therapy is to use stem cells to treat or prevent diseases or condition, which has been widely applied in the treatment of hematological diseases, cancers, cardiovascular and cerebrovascular diseases [12][13][14][15] . In addition, bone marrow transplant is one of the most widely used stem-cell therapy.
    [Show abstract] [Hide abstract] ABSTRACT: Biotherapy mainly refers to the intervention and the treatment of major diseases with biotechnologies or bio-drugs, which include gene therapy, immunotherapy (vaccines and antibodies), bone marrow transplantation and stem-cell therapy. In recent years, numerous biomaterials have emerged and were utilized in the field of biotherapy due to their biocompatibility and biodegradability. Generally, biomaterials can be classified into natural or synthetic polymers according to their source, both of which have attracted much attention. Notably, biomaterials-based non-viral gene delivery vectors in gene therapy are undergoing rapid development with the emergence of surface-modified or functionalized materials. In immunotherapy, biomaterials appear to be attractive means for enhancing the delivery efficacy and the potency of vaccines. Additionally, hydrogels and scaffolds are ideal candidates in stem-cell therapy and tissue engineering. In this review, we present an introduction of biomaterials used in above biotherapy, including gene therapy, immunotherapy, stem-cell therapy and tissue engineering. We also highlighted the biomaterials which have already entered the clinical evaluation
    Full-text · Article · Mar 2016
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