Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury

Manley, Nathan C.; Priest, Catherine A.; Denham, Jerrod; Wirth, Edward D.; Lebkowski, Jane

doi:10.1002/sctm.17-0065

Cited by 100 publications

(76 citation statements)

References 46 publications

(83 reference statements)

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“…A critical feature of the derived cells is the myelination capacity that can be assessed either in vitro using oligodendroglial‐neuronal co‐cultures or nanofibers mimicking axons (Pedraza et al, ; Stacpoole et al, ; Sundberg et al, ; Wang et al, ) or in vivo by transplantation experiments (Izrael et al, ). Additionally, a wealth of studies exploited in vivo myelination assays to demonstrate the use of ESC derived OPC as a cell‐based therapeutic strategy after irradiation therapy (Piao et al, ) or spinal cord injury (Keirstead et al, ; Kim et al, ; Manley, Priest, Denham, Wirth 3rd, & Lebkowski, ; Nistor et al, ; Sharp, Frame, Siegenthaler, Nistor, & Keirstead, ).…”

Section: Generation Of Oligodendrocytes From Pluripotent Cellsmentioning

confidence: 99%

Stem cell derived oligodendrocytes to study myelin diseases

Chanoumidou

Mozafari

Evercooren

et al. 2019

Glia

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Oligodendroglial pathology is central to de‐ and dysmyelinating, but also contributes to neurodegenerative and psychiatric diseases as well as brain injury. The understanding of oligodendroglial biology in health and disease has been significantly increased during recent years by experimental in vitro and in vivo preclinical studies as well as histological analyses of human tissue samples. However, for many of these diseases the underlying pathology is still not fully understood and treatment options are frequently lacking. This is at least partly caused by the limited access to human oligodendrocytes from patients to perform functional studies and drug screens. The induced pluripotent stem cell technology (iPSC) represents a possibility to circumvent this obstacle and paves new ways to study human disease and to develop new treatment options for so far incurable central nervous system (CNS) diseases. In this review, we summarize the differences between human and rodent oligodendrocytes, provide an overview of the different techniques to generate oligodendrocytes from human progenitor or stem cells and describe the results from studies using iPSC derived oligodendroglial lineage cells. Furthermore, we discuss future perspectives and challenges of the iPSC technology with respect to disease modeling, drug screen, and cell transplantation approaches.

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Section: Generation Of Oligodendrocytes From Pluripotent Cellsmentioning

confidence: 99%

Stem cell derived oligodendrocytes to study myelin diseases

Chanoumidou

Mozafari

Evercooren

et al. 2019

Glia

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“…Over the past two decades, many studies have evaluated the therapeutic potential of transplanting human NS/PCs or oligodendrocyte progenitor cells (OPCs), the intermediary progenitors between NS/PCs and mature oligodendrocytes (Fig. ), to regenerate CNS tissues after injury . While NS/PCs can become neurons, astrocyte or oligodendrocytes, OPCs are restricted to the oligodendrocyte lineage.…”

Section: Introductionmentioning

confidence: 99%

“…While NS/PCs can become neurons, astrocyte or oligodendrocytes, OPCs are restricted to the oligodendrocyte lineage. Differentiation of transplanted NS/PCs toward oligodendrocytes has led to significant gains in functional recovery in rodent models of spinal cord injury . Furthermore, transplantation of OPCs has shown some promise for spinal cord injury repair in recent clinical trials .…”

Section: Introductionmentioning

confidence: 99%

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Seidlits

Liang

Bierman

et al. 2019

J Biomedical Materials Res

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Neural stem/progenitor cell (NS/PC)‐based therapies have shown exciting potential for regeneration of the central nervous system (CNS) and NS/PC cultures represent an important resource for disease modeling and drug screening. However, significant challenges limiting clinical translation remain, such as generating large numbers of cells required for model cultures or transplantation, maintaining physiologically representative phenotypes ex vivo and directing NS/PC differentiation into specific fates. Here, we report that culture of human NS/PCs in 3D, hyaluronic acid (HA)‐rich biomaterial microenvironments increased differentiation toward oligodendrocytes and neurons over 2D cultures on laminin‐coated glass. Moreover, NS/PCs in 3D culture exhibited a significant reduction in differentiation into reactive astrocytes. Many NS/PC‐derived neurons in 3D, HA‐based hydrogels expressed synaptophysin, indicating synapse formation, and displayed electrophysiological characteristics of immature neurons. While inclusion of integrin‐binding, RGD peptides into hydrogels resulted in a modest increase in numbers of viable NS/PCs, no combination of laminin‐derived, adhesive peptides affected differentiation outcomes. Notably, 3D cultures of differentiating NS/PCs were maintained for at least 70 days in medium with minimal growth factor supplementation. In sum, results demonstrate the use of 3D, HA‐based biomaterials for long‐term expansion and differentiation of NS/PCs toward oligodendroglial and neuronal fates, while inhibiting astroglial fates. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 704–718, 2019.

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“…Stem cell‐based therapy, especially BMSCs, has yielded encouraging results . BMSCs transplantation therapy is promising in mitigating the extent of SCI, not only due to a favorable ethical profile and safety, but also due to providing beneficial effects on various postinjury aspects: inflammation, apoptosis, axonal regrowth, angiogenesis, tissue sparing, astroglial scar, and motor recovery .…”

Section: Introductionmentioning

confidence: 99%

“…Stem cell-based therapy, especially BMSCs, has yielded encouraging results. [5][6][7][8] BMSCs transplantation therapy is promising in mitigating the extent of SCI, not only due to a favorable ethical profile and safety, but also due to providing beneficial effects on various postinjury aspects: inflammation, apoptosis, axonal regrowth, angiogenesis, tissue sparing, astroglial scar, and motor recovery. [9][10][11][12] It is well known that BMSCs secrete a large variety of molecules and many studies have shown beneficial impacts from these factors such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), and more.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells stimulated with low‐intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury

Ning

Song

et al. 2018

CNS Neurosci Ther

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Summary Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low‐intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS‐BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS‐BMSCs postinjury, locomotor function was significantly improved in LIPUS‐BMSCs transplantation group with higher level of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS‐BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS‐BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI.

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Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury

Cited by 100 publications

References 46 publications

Stem cell derived oligodendrocytes to study myelin diseases

Stem cell derived oligodendrocytes to study myelin diseases

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Bone marrow mesenchymal stem cells stimulated with low‐intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury

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