Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke

Tanaka

et al. 2020

IJMS

Self Cite

Ischemic stroke caused by cerebral artery occlusion induces neurological deficits because of cell damage or death in the central nervous system. Given the recent therapeutic advances in reperfusion therapies, some patients can now recover from an ischemic stroke with no sequelae. Currently, reperfusion therapies focus on rescuing neural lineage cells that survive in spite of decreases in cerebral blood flow. However, vascular lineage cells are known to be more resistant to ischemia/hypoxia than neural lineage cells. This indicates that ischemic areas of the brain experience neural cell death but without vascular cell death. Emerging evidence suggests that if a vascular cell-mediated healing system is present within ischemic areas following reperfusion, the therapeutic time window can be extended for patients with stroke. In this review, we present our comments on this subject based upon recent findings from lethal ischemia following reperfusion in a mouse model of stroke.

Section: Findings After Early Reperfusion Under Lethal Ischemia Inmentioning

confidence: 86%

Section: Findings After Early Reperfusion Under Lethal Ischemia Inmentioning

confidence: 86%

How Long Are Reperfusion Therapies Beneficial for Patients after Stroke Onset? Lessons from Lethal Ischemia Following Early Reperfusion in a Mouse Model of Stroke

Tanaka

et al. 2020

IJMS

Self Cite

“…Involvement of endogenous stem cells in adult neurogenesis has repeatedly been reported in the CNS. Takagi et al () and Tatebayashi et al () demonstrated that ischaemic pericytes serve as endogenous stem cells that give rise to neurons in the poststroke region. Although we could not identify the lineage of endogenous stem cells in the nerve graft, the use of green rats as donors allowed clear demonstration of neurogenesis within the peripheral nerve that occurred through collaboration between endogenous and exogenous stem cells.…”

Section: Discussionmentioning

confidence: 99%

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion

Nakano

Kurimoto

Kato

et al. 2018

J Tissue Eng Regen Med

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 μm , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle.

“…Increasing evidence shows that multipotent neural precursors (NPCs) in the injury site not only migrate from the lateral ventricle subventricular zone (SVZ) in adult brain ( Jin et al., 2003 , Dibajnia and Morshead, 2013 ) but are also reprogrammed from local non-neuronal cells following stroke ( Shimada et al., 2012 , Nakagomi et al., 2015 ). Pericytes that wrap endothelial cells in the capillaries have emerged as an attractive cell resource, which can be reprogrammed to tissue-specific stem cells following injury ( Dellavalle et al., 2011 , Tatebayashi et al., 2017 ). In stroke-related brain injury, a mesenchymal-epithelial transition process is involved in cellular reprogramming of pericytes to multipotent NPCs ( Nakagomi et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and Functional Recovery

et al. 2017

SummaryEpigenetic modifications have emerged as attractive molecular substrates that integrate extrinsic changes into the determination of cell identity. Since stroke-related brain damage releases micro-environmental cues, we examined the role of a signaling-induced epigenetic pathway, an atypical protein kinase C (aPKC)-mediated phosphorylation of CREB-binding protein (CBP), in post-stroke neurovascular remodeling. Using a knockin mouse strain (CbpS436A) where the aPKC-CBP pathway was defective, we show that disruption of the aPKC-CBP pathway in a murine focal ischemic stroke model increases the reprogramming efficiency of ischemia-activated pericytes (i-pericytes) to neural precursors. As a consequence of enhanced cellular reprogramming, CbpS436A mice show an increased transient population of locally derived neural precursors after stroke, while displaying a reduced number of i-pericytes, impaired vascular remodeling, and perturbed motor recovery during the chronic phase of stroke. Together, this study elucidates the role of the aPKC-CBP pathway in modulating neurovascular remodeling and functional recovery following focal ischemic stroke.