scholarly journals Effects of Administration Route on Migration and Distribution of Neural Progenitor Cells Transplanted into Rats with Focal Cerebral Ischemia, an MRI Study

2009 ◽  
Vol 30 (3) ◽  
pp. 653-662 ◽  
Author(s):  
Lian Li ◽  
Quan Jiang ◽  
Guangliang Ding ◽  
Li Zhang ◽  
Zheng Gang Zhang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Focal Cerebral Ischemia ◽  
Three Dimensional ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Blue Staining ◽  
Ischemic Lesion ◽  
Administration Routes ◽  
Male Wistar Rats

We tested the hypotheses that administration routes affect the migration and distribution of grafted neural progenitor cells (NPCs) in the ischemic brain and that the ischemic lesion plays a role in mediating the grafting process. Male Wistar rats ( n=41) were subjected to 2-h middle cerebral artery occlusion (MCAo), followed 1 day later by administration of magnetically labeled NPCs. Rats with MCAo were assigned to one of three treatment groups targeted for cell transplantation intra-arterially (IA), intracisternally (IC), or intravenously (IV). MRI measurements consisting of T2-weighted imaging and three-dimensional (3D) gradient echo imaging were performed 24 h after MCAo, 4 h after cell injection, and once a day for 4 days. Prussian blue staining was used to identify the labeled cells, 3D MRI to detect cell migration and distribution, and T2 map to assess lesion volumes. Intra-arterial (IA) administration showed significantly increased migration, a far more diffuse distribution pattern, and a larger number of transplanted NPCs in the target brain than IC or IV administration. However, high mortality with IA delivery (IA: 41%; IC: 17%; IV: 8%) poses a serious concern for using this route of administration. Animals with smaller lesions at the time of transplantation have fewer grafted cells in the parenchyma.

scholarly journals Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210

2020 ◽  
Vol 6 (3) ◽  
Author(s):  
Leila Arab ◽  
Aslan Fanni ◽  
Shiva Nemati ◽  
Ehsan Arefian ◽  
Jafar Ai ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Cell Group ◽  
Ischemic Lesion ◽  
Ischemic Region ◽  
Neurological Score ◽  
Cerebral Artery Occlusion

Objective: In this study, we evaluated the effects of human embryonic derived neural progenitor cells on neurological score, histopathological changes, and miRNA-210 as biomarkers of regeneration. Methods: The animals were randomly divided into the four groups: Sh (sham), MCAO (middle cerebral artery occlusion), MCAO+PBS, MCAO+Cell. One day after MCAO induction, embryonic derived neural progenitor cells (hESC-NPCsGFP) or PBS were injected intracerebroventriculary in MCAO+Cell or MCAO+PBS groups. On day 1, 2, 3, and 7 after ischemia induction, the neurological score was tested in each rat. At 48h, the expression of miRNA-210 was evaluated and 7 days after, the pathological assessments were performed by H&E staining. Results: Neurological score showed the promotion of functional recovery in MCAO+Cell group. Based on H&E staining, the percentage of neural death in ischemic region reduced in MCAO+Cell group. The miRNA-210 significantly upregulated in both brain and blood samples. Conclusion: According to the findings, hESC-NPCsGFP injection could up-regulate the miRNA-210 of tissue and blood to support the neuroprotective and regenerative effect of hESC-NPCsGFP in the ischemic lesion and improved the neurological score and reduce the neural death in ischemic region.

scholarly journals Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon

2018 ◽  
Vol 43 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Kanako Saito ◽  
Ryotaro Kawasoe ◽  
Hiroshi Sasaki ◽  
Ayano Kawaguchi ◽  
Takaki Miyata
Keyword(s):  
Progenitor Cells ◽  
Neural Tube ◽  
Neural Progenitor Cells ◽  
Three Dimensional ◽  
Neural Progenitor ◽  
Hippo Signaling ◽  
Apical Surface ◽  
Elevated Expression ◽  
Underlying Mechanisms ◽  
The Brain

Abstract Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.

scholarly journals The Promoted Generation of Basal Forebrain Cholinergic Neurons from Neural Progenitor Cells on Three-dimensional Graphene foam Scaffold

2021 ◽  
Author(s):  
Ziyun Jiang ◽  
Lingyan Yang ◽  
Linhong Zhou ◽  
Miao Xiao ◽  
Sancheng Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progenitor Cells ◽  
Basal Forebrain ◽  
Neural Progenitor Cells ◽  
Three Dimensional ◽  
Cholinergic Neurons ◽  
Neural Progenitor ◽  
Graphene Foam ◽  
Basal Forebrain Cholinergic Neurons

Abstract Background: An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a common property of Alzheimer’s disease and the generation of functional BFCNs is related to learning and memory deficits. As a biocompatible and conductive scaffold for growth of neural stem cells, three-dimensional graphene foam (3D-GF) supports applications in tissue engineering and regenerative medicine. Although its effects on differentiation have been demonstrated, the effect of 3D-GF scaffold on the generation of BFCNs still remains unknown. Methods: In this study, we used 3D-GF as a culture substrate for neural progenitor cells (NPCs) and demonstrated that this scaffold material promotes the differentiation of BFCNs while maintaining excellent cell viability and proliferation. Results: Immunofluorescence analysis, RT-PCR, western blotting and ELISA revealed that the efficiency of BFCN differentiation on 3D-GF was significantly greater than that on tissue culture polystyrene substrates. Furthermore, a cell adhesion study suggested that 3D-GF scaffold enhances the expression of adhesion proteins including vinculin, integrin and N-cadherin. These findings indicate that 3D-GF scaffold materials are excellent candidates for the differentiation of BFCNs from NPCs. Conclusion: These results suggest new opportunities for the application of 3D-GF scaffold as a neural scaffold for Alzheimer’s disease therapies based on NPCs. Trial registration: Not applicable.

Abstract 2976: Sildenafil Enhances Neurogenesis And Oligodendrogenesis In The Ischemic Brain Of Aged Mouse

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Rui Lan Zhang ◽  
Michael Chopp ◽  
Cynthia Roberts ◽  
Min Wei ◽  
Xinli Wang ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Pde5 Inhibitor ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Immunofluorescent Staining ◽  
Aged Mouse ◽  
Ischemic Brain ◽  
Physics Department

Sildenafil enhances neurogenesis and oligodendrogenesis in the ischemic brain of aged mouse Rui Lan Zhang 1 , Michael Chopp 1,2 Cynthia Roberts 1 , Min Wei 1 , Xinli Wang 1 , Xianshuang Liu 1 , Zheng Gang Zhang 1 Departments of 1 Neurology and Henry Ford Hospital, Detroit, MI, USA 2 Oakland University, Physics Department, Rochester, MI, USA. Background and Purpose: Nestin lineage neural progenitor cells contribute to neurogenesis in adult rodent brain under non-ischemic and ischemic conditions. The present study investigated the effect of sildenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, on nestin lineage neural progenitor cells in the aged mouse after stroke. Methods: Male Nestin-CreER T2 ;R26R-stop-YFP mice at age 16 months were used. Tamoxifen was daily injected for 5 days to activate Cre/loxP system under control of the nestin promoter, leading to permanent YFP labeling of nestin lineage cells. These mice were subjected to permanent middle cerebral artery occlusion (MCAo) 14 days after the last tamoxifen injection. Sildenafil at 10mg/kg (n=11) or saline (n=10) was aadministered daily for 7 days starting 1 day after MCAo. All mice were sacrificed 30 days after MCAo. The number of nestin lineage cells and their fate were analyzed using immunohistochemistry staining. Results: Double immunofluorescent staining confirmed YFP positive cells were nestin positive. Unbiased stereological analysis revealed that sildenafil treatment significantly increased (p<0.05) the number of nestin linage cells in the ischemic subventricular zone (SVZ, 803 ± 28 vs 657 ± 41 in saline), striatum (3739 ± 162 vs 3029 ± 144 in saline), and corpus callosum (2957 ± 86 vs 2578 ± 117 in saline). Phenotype analysis showed that sildenafil substantially augmented the number of nestin lineage neuroblasts identified by doublecortin positive cells (19.4 ± 1.6 % vs 12.9 ± 1.1 % in saline), nestin lineage mature neurons measured by NeuN (6.2 ± 0.8 % vs 3.0 ± 0.6 %) and calbindin (10.8 ± 0.9 vs 7.2 ± 1.1) positive cells in the ischemic striatum. Sildenafil also significantly (p<0.05) increased the number of nestin lineage oligodendrocytes measured by 2’, 3’-cyclic nucleotide, 3’-phosphodiesterase (CNPase) positive cells in ischemic striatum (21.3 ± 1.2 vs 19.9 ± 1.4 in saline) and corpus callosum (18.9 ± 1.4 vs 14.4 ± 1.3 in saline). Conclusion: Our data demonstrate that sildenafil enhances neurogenesis and oligodendrogenesis in the ischemic brain of the aged mouse, which could contribute sildenafil-improved neurological outcome after stroke which we have demonstrated.

Abstract 133: Transplantation Of Neurosphere-forming Stem Cells Into Circulating Blood Attenuates Acute Inflammatory Activation Of Both Brain And Spleen After Cerebrovascular Ischemic Injury.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Soon-Tae Lee ◽  
Kon Chu ◽  
Keun-Hwa Jung ◽  
Hee-Kwon Park ◽  
Jeong-Min Kim ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Progenitor Cells ◽  
Inflammatory Cytokines ◽  
Neural Progenitor Cells ◽  
Focal Cerebral Ischemia ◽  
Neural Progenitor ◽  
Control Group ◽  
Tissue Ischemia ◽  
Realtime Pcr ◽  
Inflammatory Activation

Background and Objectives: Transplantation of neural progenitor cells (NPCs) has been studied to achieve the regeneration of damaged brain in experimental stroke models. Tissue ischemia induces systemic inflammatory activation, especially in spleen. However, the interaction between NPCs and immune/inflammatory cells has not been studied in ischemia models. In this study, we investigated whether NPC can attenuate cerebral and systemic inflammatory activation in focal cerebral ischemia. Methods: Focal cerebral ischemia was induced by intraluminal thread occlusion of the middle cerebral artery for 60 minutes (c57/bl6 adult male mice), and mouse NPC from primary neurosphere (1 million cells) or vehicle (PBS, control group) was injected via tail veins with cerebral reperfusion. Inflammatory cytokines were evaluated with RealTime-PCR at 22 hrs, and the weights of each spleen and thymus were measured. Results: Cerebral ischemia induced progressive atrophies of spleen and thymus when measured at 22 hr and 96 hr after ischemia. Intravenous injection of NPC accelerated these lymphoid organ atrophies, and the weights of spleen and thymus were significantly lower in NPC-injected mice at 96 hr after the ischemia compared to the vehicle injected mice. RealTime-PCR analysis using ischemic hemispheres and spleens showed reduced expressions of inflammatory cytokines, including TNF-alpha, IL-6, MIP-2, IL-13, FoxP3, IL-1beta, and IP10 in NPC-injected brains and spleens at 22 hr after the ischemia. Transplanted NPCs were detected in systemic organs, and mostly in spleen. NPC-injected mice showed reduced infarct volume and neurologic deficits. Conclusion: Intravenous transplantation of primary neuro-sphere cells in cerebral ischemia attenuated systemic inflammatory activation, which suggests that the immunomodulating property of neural progenitor cells can be applicable for preventing harmful inflammations after the tissue ischemia.

Abstract 141: The Microrna 17-92 Cluster in Neural Progenitor Cells is Required for Stroke-induced Neurogenesis and Gliogenesis

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wanlong Pan ◽  
Xianshuang Liu ◽  
Xiaoming Zhang ◽  
Xinli Wang ◽  
Jiani Hu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Tamoxifen Treatment ◽  
Oligodendrocyte Progenitor Cells ◽  
Factor Inhibitor

Background: Molecular mechanisms underlying stroke-induced neurogenesis have not been fully investigated. The microRNA 17-92 cluster (miR17-92) regulates proliferation and differentiation of adult neural progenitor cells (NPCs). The present study investigated whether the miR17-92 cluster in NPCs is required for stroke-induced neurogenesis. Methods and Results: Mice with inducible and conditional knockdown of the miR17-92 cluster in nestin lineage NPCs (nestin-CreER T2 /miR17-92 -/- , 17-92-cKO, n=9) and wild-type litters (WT, n=9) were treated by tamoxifen. Administration of tamoxifen resulted in more than 60% reduction of individual members of the miR-17-92 cluster (miR-17: 1.0 vs 0.4; miR-19a: 1.0 vs 0.3; miR-19b: 1.0 vs 0.2; miR-20a: 1.0 vs 0.4; miR-92a: 1.0 vs 0.4 fold in WT, p<0.05) in NPCs localized to the subventricular zone (SVZ). Two days after termination of tamoxifen treatment, these mice were subjected to permanent right middle cerebral artery occlusion (MCAO) and sacrificed 28 days post-MCAo. Compared to WT mice, 17-92-cKO mice exhibited significant (p<0.05) reduction of proliferation of NPCs measured by the number of Ki67 + cells (226±43 vs 471±100 cells/mm 2 ) and the number of DCX + neuroblasts (11±2% vs 24±4% ) in the ischemic SVZ. Cultured NPCs harvested from ischemic cKO mice showed significant (p<0.05) reduction of BrdU + cells (37±2% vs 61±4% WT , n=3/group), Tuj1 + neuroblasts (5±0.2% vs 9±0.4% ), GFAP + cells (33±3% vs 53±2% ), and NG2 + oligodendrocyte progenitor cells (OPCs, 3±0.1% vs 5±0.5%). These in vivo and in vitro data indicate that reduction of the miR17-92 cluster suppresses stroke-induced neurogenesis and gliogenesis. Western blot analysis showed that miR17-92 cKO significantly (p<0.05) increased and reduced a cytoskeleton-associated protein, Enigma homolog1 (ENH1, 1.6 vs 1.0 fold), and its down-stream transcription factor, inhibitor of differentiation1 (ID1, 1.0 vs 0.6 fold), respectively. ENH1 is a putative target of the miR17-92 cluster. Conclusion: Our data indicate that the miR17-92 cluster in adult nestin lineage NPCs is required for stroke-induced neurongenesis and gliogenesis, and that the miR17-92 cluster possibly targets ENH1/ID1 signaling.

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