The in vivo timeline of differentiation of engrafted human neural progenitor cells

Vogel, Stefanie N.; Schäfer, Cordula; Heß, Simon; Folz-Donahue, Kat; Nelles, Melanie; Minassian, Anuka; Schwarz, Martin K.; Kukat, Christian; Ehrlich, Marc; Zaehres, Holm; Kloppenburg, Peter; Hoehn, Mathias; Aswendt, Markus

doi:10.1016/j.scr.2019.101429

Cited by 13 publications

(11 citation statements)

References 41 publications

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“…The immunohistochemical analysis allowed no detection of grafted cells differentiated into GFAP + astrocytes or NeuN + neurons. In contrast to our findings, Vogel et al (2019) had described that the majority of grafted hNSCs had differentiated into the glial lineage by 3 months when implanted into healthy brains of nude mice while these authors found only very few neurons. This difference may be explained by the fact that the human stem cells were not the H9-derived NSCs used here but of a different origin and were implanted only into the healthy cortex of nude mice.…”

Section: Monitoring the Graft Fatecontrasting

confidence: 99%

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Human Neural Stem Cell Induced Functional Network Stabilization After Cortical Stroke: A Longitudinal Resting-State fMRI Study in Mice

Minassian

Green

Diedenhofen

et al. 2020

Front. Cell. Neurosci.

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Most stroke studies dealing with functional deficits and assessing stem cell therapy produce extensive hemispheric damage and can be seen as a model for severe clinical strokes. However, mild strokes have a better prospect for functional recovery. Recently, anatomic and behavioral changes have been reported for distal occlusion of the middle cerebral artery (MCA), generating a well-circumscribed and small cortical lesion, which can thus be proposed as mild to moderate cortical stroke. Using this cortical stroke model of moderate severity in the nude mouse, we have studied the functional networks with resting-state functional magnetic resonance imaging (fMRI) for 12 weeks following stroke induction. Further, human neural stem cells (hNSCs) were implanted adjacent to the ischemic lesion, and the stable graft vitality was monitored with bioluminescence imaging (BLI). Differentiation of the grafted neural stem cells was analyzed by immunohistochemistry and by patch-clamp electrophysiology. Following stroke induction, we found a pronounced and continuously rising hypersynchronicity of the sensorimotor networks including both hemispheres, in contrast to the severe stroke filament model where profound reduction of the functional connectivity had been reported by us earlier. The vitality of grafted neural stem cells remained stable throughout the whole 12 weeks observation period. In the stem cell treated animals, functional connectivity did not show hypersynchronicity but was globally slightly reduced below baseline at 2 weeks post-stroke, normalizing thereafter completely. Our resting-state fMRI (rsfMRI) studies on cortical stroke reveal for the first time a hypersynchronicity of the functional brain networks. This hypersynchronicity appears as a hallmark of mild cortical strokes, in contrast to severe strokes with striatal involvement where exclusively hyposynchronicity has been reported. The effect of the stem cell graft was an early

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Section: Monitoring the Graft Fatecontrasting

confidence: 99%

“…Whole-cell patch-clamp recordings were essentially performed as described previously (Tennstaedt et al, 2015a;Vogel et al, 2019). Details are provided in the Supplementary File 1.…”

Section: Electrophysiological Measurementsmentioning

confidence: 99%

Human Neural Stem Cell Induced Functional Network Stabilization After Cortical Stroke: A Longitudinal Resting-State fMRI Study in Mice

Minassian

Green

Diedenhofen

et al. 2020

Front. Cell. Neurosci.

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“…In fact, light-sheet microscopy has contributed to not only the discovery of principles of early development, as described above [20,28,29,41], but also to biomaterial development, tissue engineering, and regenerative medicine. For example, the movement and morphology of mesenchymal stem cells and tumor cells over the surface of a spherical microcarrier [45][46][47] and the differentiation and connection with host neurons of transplanted human cells in whole mouse brain [48,49] were visualized to advance medical applied research.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Digital Spindle: A New Way to Explore Mitotic Functions by Whole Cell Data Collection and a Computational Approach

Yamashita

Murakami

Yokota

et al. 2020

Cells

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From cells to organisms, every living system is three-dimensional (3D), but the performance of fluorescence microscopy has been largely limited when attempting to obtain an overview of systems’ dynamic processes in three dimensions. Recently, advanced light-sheet illumination technologies, allowing drastic improvement in spatial discrimination, volumetric imaging times, and phototoxicity/photobleaching, have been making live imaging to collect precise and reliable 3D information increasingly feasible. In particular, lattice light-sheet microscopy (LLSM), using an ultrathin light-sheet, enables whole-cell 3D live imaging of cellular processes, including mitosis, at unprecedented spatiotemporal resolution for extended periods of time. This technology produces immense and complex data, including a significant amount of information, raising new challenges for big image data analysis and new possibilities for data utilization. Once the data are digitally archived in a computer, the data can be reused for various purposes by anyone at any time. Such an information science approach has the potential to revolutionize the use of bioimage data, and provides an alternative method for cell biology research in a data-driven manner. In this article, we introduce examples of analyzing digital mitotic spindles and discuss future perspectives in cell biology.

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“…• Different stages of NSC differentiation monitored with a luciferase responsive to microtubule-associated protein 2, glial fibrillary acidic protein, and myelin proteolipid protein [45] • Detection of early-and late-stage neuronal differentiation using a luciferase responsive to doublecortin and synapsin 1 [ 120] (Continued)…”

Section: Survival Human Ascsmentioning

confidence: 99%

“…[113] Vogel et al [45] developed a BLI toolkit that can monitor in vivo neuro-and gliogenesis with a luciferase gene controlled by promoters for microtubule-associated protein 2, glial fibrillary acidic protein, and myelin proteolipid protein, which are cellspecific markers for neurons, astrocytes, and oligodendrocytes, respectively. [114][115][116] When Vogel et al [45] implanted hNSCs transduced with these constructs into the brains of immunodeficient mice, they observed an increase in luminescence from myelin proteolipid protein-driven Fluc, microtubule-associated protein 2-driven Fluc, and glial fibrillary acidic protein-driven luc2 until 4, 6, and 12 weeks post-transplantation, respectively. This pattern of luminescence is consistent with progenitor differentiation to both neurons and astrocytes, but low levels of glial differentiation to oligodendrocytes over 12 weeks.…”

Section: Neuro-and Gliogenesismentioning

confidence: 99%

Illuminating the Regenerative Properties of Stem Cells In Vivo with Bioluminescence Imaging

Madsen

Giler

Bunnell

et al. 2020

Biotechnology Journal

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Preclinical animal studies are essential to the development of safe and effective stem cell therapies. Bioluminescence imaging (BLI) is a powerful tool in animal studies that enables the real-time longitudinal monitoring of stem cells in vivo to elucidate their regenerative properties. This review describes the application of BLI in preclinical stem cell research to address critical challenges in producing successful stem cell therapeutics. These challenges include stem cell survival, proliferation, homing, stress response, and differentiation. The applications presented here utilize bioluminescence to investigate a variety of stem and progenitor cells in several different in vivo models of disease and implantation. An overview of luciferase reporters is provided, along with the advantages and disadvantages of BLI. Additionally, BLI is compared to other preclinical imaging modalities and potential future applications of this technology are discussed in emerging areas of stem cell research.

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The in vivo timeline of differentiation of engrafted human neural progenitor cells

Cited by 13 publications

References 41 publications

Human Neural Stem Cell Induced Functional Network Stabilization After Cortical Stroke: A Longitudinal Resting-State fMRI Study in Mice

Human Neural Stem Cell Induced Functional Network Stabilization After Cortical Stroke: A Longitudinal Resting-State fMRI Study in Mice

Digital Spindle: A New Way to Explore Mitotic Functions by Whole Cell Data Collection and a Computational Approach

Illuminating the Regenerative Properties of Stem Cells In Vivo with Bioluminescence Imaging

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