Stem Cell–Based Tissue Replacement After Stroke

Janowski, Mirosław; Wagner, Daniel; Boltze, Johannes

doi:10.1161/strokeaha.114.007803

Cited by 85 publications

(33 citation statements)

References 105 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the network stabilization points to a paracrine effect of the NSCs secreting growth factors and cytokines. Our interpretation of the stem cells acting via paracrine effect is in line with the findings of a recent study discussing modification of the excitatory-inhibitory balance caused by the paracrine effect of NPCs transplanted 3 d after stroke in mice, and reflects the growing consensus that the therapeutic value of stem cells for stroke lies in their growth factor-mediated and immunomodulation-mediated neuroprotective potential (Guzman, 2009;Janowski et al, 2015).…”

Section: Modulation By Stem Cell Graftsupporting

confidence: 86%

“…Several experimental investigations have already reported outcome improvement after stem cell implantation in rodent models of stroke (Bacigaluppi et al, 2009;Minnerup et al, 2011;Doeppner et al, 2017). The attention of those studies has typically been limited to the ischemic focus itself assessing e.g., lesion size or has been drawn to the fate of the stem cell graft, e.g., structural and functional integration into the host brain tissue, while correlating these aspects with behavioral deficit and improvement, respectively (Ramos-Cabrer et al, 2010;Oki et al, 2012;Tornero et al, 2013).…”

Section: Significance Statementmentioning

confidence: 99%

“…High angular resolution diffusion imaging maps the underlying neural pathways through the reconstruction of axonal bundles (fibers). Also, the spherical harmonics-based Q-ball reconstruction algorithm (Tuch, 2004;Descoteaux et al, 2007) allows researchers to accurately resolve regions with a rather complex fiber architecture that involves multiple fiber directions within one voxel (Tuch et al, 2003). Thus, we have looked at the changes in fiber density of the sensorimotor structural pathways.…”

Section: Significance Statementmentioning

confidence: 99%

“…In addition to the ROIs used for the functional datasets, we included the following white matter regions: cerebral peduncle (cp), corpus callosum (cc), fimbria (fi), fornix (fx), internal capsule (ic), and the anterior commissure (ac). Diffusion data were reconstructed with DSIStudio (dsi-studio.labsolver.org) by using spherical harmonics-based Q-ball reconstruction (Tuch, 2004;Descoteaux et al, 2007) with a regularization parameter of 0.006 (Descoteaux et al, 2007) and eightfold tessellation. Quantitative anisotropy maps were calculated and group-wise averaged, then ROI-based analysis was conducted with ImageJ using custom macros (Version 1.46; National Institutes of Health, Bethesda, MD; http://rsbweb.nih.gov/ij).…”

Section: Data Processingmentioning

confidence: 99%

See 3 more Smart Citations

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain

et al. 2018

View full text Add to dashboard Cite

Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft However, an assessment of the long-term functional and structural improvement is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of their influence on the whole-brain networks. Here, we have longitudinally and noninvasively monitored the structural and functional network alterations in the mouse model of focal cerebral ischemia. Structural changes of fiber-density increases are stimulated in the endogenous tissue without further modulation by the stem cells, while functional networks are stabilized by the stem cells via a paracrine effect. These results will help decipher the underlying networks of brain plasticity in response to cerebral lesions and offer clues to unravelling the mystery of how stem cells mediate regeneration.

show abstract

Section: Modulation By Stem Cell Graftsupporting

confidence: 86%

Section: Significance Statementmentioning

confidence: 99%

Section: Significance Statementmentioning

confidence: 99%

Section: Data Processingmentioning

confidence: 99%

See 2 more Smart Citations

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Thus, alternative therapeutic strategies with a wide therapeutic window are highly desirable. Recently, stem cell‐based therapy has emerged as such a strategy, which is characterized by a wide therapeutic window and can be convergent with rehabilitation . Neural stem cell (NSC) transplantation not only remodels the CNS by promoting neuroplasticity, angiogenesis, and immunomodulation, but also generates neurons to replace the lost neuronal circuitry.…”

Section: Introductionmentioning

confidence: 99%

MRI‐Visible siRNA Nanomedicine Directing Neuronal Differentiation of Neural Stem Cells in Stroke

Wang

Zhang

et al. 2018

Adv Funct Materials

View full text Add to dashboard Cite

A major challenge in stroke treatment is the restoration of neural circuit in which neuron function plays a central role. Although transplantation of exogenous neural stem cells (NSCs) is admittedly a promising therapeutical means, the treatment outcome is greatly affected due to the poor NSCs differentiation into neurons caused by myelin associated inhibitory factors binding to Nogo-66 receptor (NgR). Herein, a nanoscale polymersome is developed to codeliver superparamagnetic iron oxide nanoparticles and siRNA targeting NgR gene (siNgR) into NSCs. This multifunctional nanomedicine directs neuronal differentiation of NSCs through silencing the NgR gene and meanwhile allows a noninvasive monitoring of NSC migration with magnetic resonance imaging. An improved recovery of neural function is achieved in rat ischemic stroke model. The results demonstrate the great potential of the multifunctional siRNA nanomedicine in stroke treatment based on stem cell transplantation.

show abstract