Enhancement of intercellular interaction between iPSC-derived neural progenitor cells and activated endothelial cells using cell surface modification with functional oligopeptides

2022 ◽  
Author(s):  
Isha Goel ◽  
Makoto Noiri ◽  
Yuka Yamauchi ◽  
Koichi Kato ◽  
Ung-il Chung ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Surface Modification ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Mechanical Thrombectomy ◽  
Treatment Options ◽  
Intercellular Interaction ◽  
Cell Based Therapy ◽  
Tissue Plasminogen

Cell-based therapy has been used to treat stroke related disorders, which have no treatment options available 4.5 hours after onset. Although the administration of tissue plasminogen activator and mechanical thrombectomy...

scholarly journals Isolation of Neural Progenitor Cells From the Human Adult Subventricular Zone Based on Expression of the Cell Surface Marker CD271

2014 ◽  
Vol 3 (4) ◽  
pp. 470-480 ◽  
Author(s):  
Miriam E. van Strien ◽  
Jacqueline A. Sluijs ◽  
Brent A. Reynolds ◽  
Dennis A. Steindler ◽  
Eleonora Aronica ◽  
...  
Keyword(s):  
Cell Surface ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Surface Marker ◽  
Cell Surface Marker ◽  
Human Adult

scholarly journals Downregulation of Neurodevelopmental Gene Expression in iPSC-Derived Cerebral Organoids Upon Infection by Human Cytomegalovirus

2021 ◽  
Author(s):  
Benjamin Shea O'Brien ◽  
Rebekah L Mokry ◽  
Megan L Schumacher ◽  
Kirthi Pulakanti ◽  
Sridhar Rao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Human Cytomegalovirus ◽  
Neural Progenitor Cells ◽  
Treatment Options ◽  
Congenital Infection ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitor ◽  
Human Neurons ◽  
The Impact

Human cytomegalovirus (HCMV) is a beta herpesvirus that, upon congenital infection, can cause severe birth defects including vision and hearing loss, microcephaly, and seizures. Currently, no approved treatment options exist for in utero infections. We previously demonstrated that HCMV infection decreases calcium signaling responses and alters neuronal differentiation in induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPCs). Here we aimed to determine the impact of infection on the transcriptome in developing human neurons using iPSC-derived 3-dimensional cerebral organoids. We infected iPSC-derived cerebral organoids with HCMV encoding eGFP and sorted cell populations based on GFP signal strength. Significant transcriptional downregulation was observed including in key neurodevelopmental gene pathways in both the GFP (+) and intermediate groups. Interestingly, the GFP (-) group also showed downregulation of the same targets indicating a mismatch between GFP expression and viral infection. Using a modified HCMV virus destabilizing IE 1 and 2 proteins, we still observed significant downregulation of neurodevelopmental gene expression in infected neural progenitor cells. Together, these data indicate that IE viral proteins are not the main drivers of neurodevelopmental gene dysregulation in HCMV infected neural tissues suggesting therapeutically targeting IE gene expression is insufficient to restore neural differentiation and function.

Bidirectional crosstalk between periventricular endothelial cells and neural progenitor cells promotes the formation of a neurovascular unit

2014 ◽  
Vol 1565 ◽  
pp. 8-17 ◽  
Author(s):  
Ravi Vissapragada ◽  
Mauricio A. Contreras ◽  
Cleide G da Silva ◽  
Vivek A. Kumar ◽  
Angelica Ochoa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neurovascular Unit ◽  
Neural Progenitor

scholarly journals Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

2007 ◽  
Vol 28 (4) ◽  
pp. 764-771 ◽  
Author(s):  
Hua Teng ◽  
Zheng Gang Zhang ◽  
Lei Wang ◽  
Rui Lan Zhang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Vascular Endothelial ◽  
Cerebral Endothelial Cells ◽  
Progenitor Cell Proliferation ◽  
Endothelial Growth Factor

Angiogenesis and neurogenesis are coupled processes. Using a coculture system, we tested the hypothesis that cerebral endothelial cells activated by ischemia enhance neural progenitor cell proliferation and differentiation, while neural progenitor cells isolated from the ischemic subventricular zone promote angiogenesis. Coculture of neural progenitor cells isolated from the subventricular zone of the adult normal rat with cerebral endothelial cells isolated from the stroke boundary substantially increased neural progenitor cell proliferation and neuronal differentiation and reduced astrocytic differentiation. Conditioned medium harvested from the stroke neural progenitor cells promoted capillary tube formation of normal cerebral endothelial cells. Blockage of vascular endothelial growth factor receptor 2 suppressed the effect of the endothelial cells activated by stroke on neurogenesis as well as the effect of the supernatant obtained from stroke neural progenitor cells on angiogenesis. These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling.

Simultaneous Isolation of Human Bone Marrow Hematopoietic, Endothelial, and Mesenchymal Progenitor Cells by Flow Sorting Based on Aldehyde Dehydrogenase Activity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3651-3651
Author(s):  
Tracy Gentry ◽  
Sandra J. Foster ◽  
Lisa Winstead ◽  
Erica Deibert ◽  
Michelle Fiordalisi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Cell Sorting ◽  
Mesenchymal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
In Cells

Abstract ALDH bright [ALDHbr] cells exhibit low side scatter and high activity of the intracellular enzyme aldehyde dehydrogenase [ALDH] in flow cytometric analysis. ALDH regulates gene expression in many developing systems by producing retinoic acids. ALDHbr populations from human umbilical cord [UCB] and mobilized peripheral blood preparations [PBSC] are highly enriched for cells that express CD34 and CD133 and for hematopoeitic progenitor cells. Because human bone marrow [BM] contains a highly heterogeneous population of stem and progenitor cells, we used multiparameter flow analysis and cell sorting to measure expression of cell surface markers and lineage specific developmental potential of BM ALDHbr populations. The ALDHbr population comprised 1.2 ± 0.8% (mean ± SD, n=39) of the nucleated BM cells and was significantly (p<0.05) enriched in cells expressing CD34, CD117, CD105, CD127, CD133, and CD166. ALDHbr populations were also significantly enriched in cells expressing primitive progenitor phenotypes including CD34+CD38− and CD34+CD133+ cells. The cell surface antigen expression of BM ALDHbr populations differed significantly from UCB and PBSC populations. In particular, the BM ALDHbr populations had more CD34− cells and CD45− cells and fewer CD133+ cells than the UCB and PBSC ALDHbr populations. Next, we compared the ability of sorted ALDHbr cells and ALDHdim cells derived from each bone marrow to develop into erythroid and myeloid cells, megakaryocytes, endothelial cells, and mesenchymal cells in culture. The ALDHdim population was the residual cell population produced when we sorted ALDHbr cells out of BM. ALDHbr populations were 144-fold more active in primary hematopoietic colony forming activity than ALDHdim cells, and all detectable BM cells that could form megakaryocyte colonies were ALDHbr. Even though hematopoietic progenitor activity was concentrated in the ALDHbr population, the majority of CD34+ and CD133+ cells in BM were ALDHdim. Cultures seeded with 50,000 ALDHbr cells gave rise to confluent growth of endothelial cells that expressed surface Ulex lectin receptors and von Willebrand factor, formed tubules on Matrigel, and took up acetylated LDL in 34 of 39 BM tested. In contrast, only 18 of 33 ALDHdim BM populations tested gave rise to endothelial cultures, and 500,000 ALDHdim cells were required to generate confluent cultures in 21 days. Cells that gave rise to early endothelial growth colonies at day 7 were 435-fold more frequent in the ALDHbr than the ALDHdim population. Confluent cultures of cells expressing cell surface antigens and functional attributes of multipotential mesenchymal cells were also routinely established with 50,000 ALDHbr cells. Again, ten-fold more ALDHdim cells than ALDHbr cells were needed to establish mesenchymal cultures. The mesenchymal cultures could be driven to differentiate into adipocytes, chondrocytes, osteoblasts, and neural lineage cells in standard culture assays. These results show that most of the hematopoietic, endothelial, and mesenchymal progenitor cell activities in human BM can be simultaneously isolated by cell sorting based on ALDH activity. Such ALDHbr populations may be useful in a variety of cell therapy indications.

scholarly journals Neural Progenitor Cells Treated with EPO Induce Angiogenesis through the Production of Vegf

2008 ◽  
Vol 28 (7) ◽  
pp. 1361-1368 ◽  
Author(s):  
Lei Wang ◽  
Michael Chopp ◽  
Sara R Gregg ◽  
Rui Lan Zhang ◽  
Hua Teng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Selective Inhibition ◽  
Neural Progenitor ◽  
Tube Formation ◽  
Human Erythropoietin ◽  
Mouse Brain Endothelial Cells

Recombinant human erythropoietin (rhEPO) induces neurogenesis and angiogenesis. Using a coculture system of mouse brain endothelial cells (MBECs) and neural progenitor cells derived from the subventricular zone of adult mouse, we investigated the hypothesis that neural progenitor cells treated with rhEPO promote angiogenesis. Treatment of neural progenitor cells with rhEPO significantly increased their expression and secretion of vascular endothelial growth factor (VEGF) and activated phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase (ERK1/2). Selective inhibition of the Akt and ERK1/2 signaling pathways significantly attenuated the rhEPO-induced VEGF expression in neural progenitor cells. The supernatant harvested from neural progenitor cells treated with rhEPO significantly increased the capillary-like tube formation of MBECs. SU1498, a specific VEGF type-2 receptor (VEGFR2) antagonist, abolished the supernatant-enhanced angiogenesis. In addition, coculture of MBECs with neural progenitor cells treated with rhEPO substantially increased VEGFR2 mRNA and protein levels in MBECs. These in vitro results suggest that EPO enhances VEGF secretion in neural progenitor cells through activation of the PI3K/Akt and ERK1/2 signaling pathways and that neural progenitor cells treated with rhEPO upregulate VEGFR2 expression in cerebral endothelial cells, which along with VEGF secreted by neural progenitor cells promotes angiogenesis.

scholarly journals Extracellular vesicle-mediated amyloid transfer to neural progenitor cells: implications for RAGE and HIV infection

2020 ◽  
Author(s):  
Ibolya E. András ◽  
Marta Garcia-Contreras ◽  
Christopher Yanick ◽  
Paola Perez ◽  
Brice Sewell ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Advanced Glycation Endproducts ◽  
Specific Inhibitor ◽  
Neural Progenitor ◽  
Extracellular Vesicle ◽  
Brain Endothelial Cells ◽  
Glycation Endproducts

Abstract Amyloid beta (Aβ) deposition was demonstrated to be elevated in the brains of HIV-infected patients and associated with neurocognitive decline; however, the mechanisms of these processes are poorly understood. The goal of the current study was to address the hypothesis that Aβ can be transferred via extracellular vesicles (ECVs) from brain endothelial cells to neural progenitor cells (NPCs) and that this process can contribute to abnormal NPC differentiation. Mechanistically, we focused on the role of the receptor for advanced glycation endproducts (RAGE) and activation of the inflammasome in these events. ECVs loaded with Aβ (Aβ-ECVs) were readily taken up by NPCs and Aβ partly colocalized with the inflammasome markers ASC and NLRP3 in the nuclei of the recipient NPCs. This colocalization was affected by HIV and RAGE inhibition by a high-affinity specific inhibitor FPS-ZM1. Blocking RAGE resulted also in an increase in ECV number produced by brain endothelial cells, decreased Aβ content in ECVs, and diminished Aβ-ECVs transfer to NPC nuclei. Interestingly, both Aβ-ECVs and RAGE inhibition altered NPC differentiation. Overall, these data indicate that RAGE inhibition affects brain endothelial ECV release and Aβ-ECVs transfer to NPCs. These events may modulate ECV-mediated amyloid pathology in the HIV-infected brain and contribute to the development of HIV-associated neurocognitive disorders.

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