Abstract TP470: Stimulation of Blood Vessel Formation by Human Neural Stem/Progenitor Cells is Mediated by Secreted Material

Human neural stem/progenitor cells (hNSPCs) have the potential to widen the current narrow treatment window for stroke as they improve functional recovery in rodent stroke models when transplanted weeks after stroke. One aspect of the hNSPC-induced functional recovery is increased angiogenesis and neovascularization in the peri-infarct region. Our lab created a human cell in vitro model of vessel formation by seeding hNSPCs and human endothelial progenitor cells (hEPCs) in a 3D scaffold composed of salmon fibrinogen, laminin, and hyaluronic acid that mimics brain tissue properties. Using our in vitro neurovascular model, we tested the hypothesis that hNSPC-secreted material plays a role in the stimulation of vessel formation. Our RNA-Seq data show that hNSPCs express high levels of secreted pro-angiogenic proteins, such as growth factors, matrix molecules, and cytokines, but hNSPCs might also impact vessel formation by secretion of extracellular vesicles or cell-contact mediated mechanisms. In order to determine the effect of hNSPC-secreted material on vessel formation, mCherry-labeled hEPCs were seeded in 3D scaffolds alone, with CellTracker Green-labeled hNSPCs, or with hNSPC-conditioned media containing hNSPC-secreted soluble factors and extracellular vesicles, such as exosomes. Vessel formation was quantified using AngioTool to determine total vessel length, number of branch points, and vessel percentage area. We found an increase in vessel formation in the presence of hNSPCs and hNSPC-conditioned media compared to hEPCs alone. In conclusion, material secreted by hNSPCs can recapitulate the increase in vessel formation induced by hNSPCs themselves. In future studies, we will determine whether hNSPC-derived exosomes are important for promoting vessel formation as they have therapeutic potential without the limitations of cell therapy.

Download Full-text

Direct Stimulation of Adult Neural Stem/Progenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B

PLoS ONE ◽

10.1371/journal.pone.0035636 ◽

2012 ◽

Vol 7 (4) ◽

pp. e35636 ◽

Cited By ~ 54

Author(s):

Pengwei Zhuang ◽

Yanjun Zhang ◽

Guangzhi Cui ◽

Yuhong Bian ◽

Mixia Zhang ◽

...

Keyword(s):

Progenitor Cells ◽

Salvianolic Acid B ◽

Direct Stimulation ◽

Salvianolic Acid ◽

Neural Stem Progenitor Cells ◽

Stimulation Of

Download Full-text

Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

Cell Transplantation ◽

10.3727/096368913x670967 ◽

2014 ◽

Vol 23 (11) ◽

pp. 1451-1464 ◽

Cited By ~ 21

Author(s):

Hiroki Iwai ◽

Satoshi Nori ◽

Soraya Nishimura ◽

Akimasa Yasuda ◽

Morito Takano ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Progenitor Cells ◽

Functional Recovery ◽

Control Group ◽

Cord Injury ◽

Neural Stem Progenitor Cells ◽

Neurotropic Factor ◽

Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

Download Full-text

Reactive astrogliosis induces astrocytic differentiation of adult neural stem/progenitor cells in vitro

Journal of Neuroscience Research ◽

10.1002/jnr.21044 ◽

2006 ◽

Vol 84 (7) ◽

pp. 1415-1424 ◽

Cited By ~ 29

Author(s):

J. Faijerson ◽

R.B. Tinsley ◽

K. Apricó ◽

A. Thorsell ◽

C. Nodin ◽

...

Keyword(s):

Progenitor Cells ◽

Reactive Astrogliosis ◽

Astrocytic Differentiation ◽

Neural Stem Progenitor Cells

Download Full-text

Evaluation of the effects of riluzole on adult spinal cord‐derived neural stem/progenitor cells in vitro and in vivo

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2015.08.007 ◽

2015 ◽

Vol 47 (Part_B) ◽

pp. 140-146 ◽

Cited By ~ 5

Author(s):

Laureen D. Hachem ◽

Andrea J. Mothe ◽

Charles H. Tator

Keyword(s):

Spinal Cord ◽

Progenitor Cells ◽

Neural Stem Progenitor Cells ◽

Adult Spinal Cord

Download Full-text

Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

Molecular Brain ◽

10.1186/1756-6606-4-35 ◽

2011 ◽

Vol 4 (1) ◽

pp. 35 ◽

Cited By ~ 13

Author(s):

Junichi Yamane ◽

Satoru Ishibashi ◽

Masanori Sakaguchi ◽

Toshihiko Kuroiwa ◽

Yonehiro Kanemura ◽

...

Keyword(s):

Progenitor Cells ◽

Brain Ischemia ◽

Functional Recovery ◽

Mongolian Gerbil ◽

Neural Stem Progenitor Cells ◽

Focal Brain Ischemia

Download Full-text

Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels

10.1101/2021.05.09.443303 ◽

2021 ◽

Author(s):

Leyla Dogan ◽

Ruben Scheuring ◽

Nicole Wagner ◽

Yuichiro Ueda ◽

Philipp Woersdoerfer ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Progenitor Cells ◽

Vessel Wall ◽

De Novo ◽

Hierarchical Organization ◽

Wall Structure ◽

Electron Microscopic ◽

Vessel Formation

Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks, or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type 1 bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimicks the embryonic steps of vessel formation by vasculogenesis. Histological evaluations at different time points of extrusion revealed initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, capillary-like vessel structures deposited a basement membrane-like matrix structure at the basal side between the vessel wall and the alginate-collagen matrix. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.

Download Full-text

Long-Term Selective Stimulation of Transplanted Neural Stem/Progenitor Cells for Spinal Cord Injury Improves Locomotor Function

SSRN Electronic Journal ◽

10.2139/ssrn.3858060 ◽

2021 ◽

Author(s):

Momotaro Kawai ◽

Kent Imaizumi ◽

Mitsuru Ishikawa ◽

Shinsuke Shibata ◽

Munehisa Shinozaki ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Progenitor Cells ◽

Locomotor Function ◽

Selective Stimulation ◽

Cord Injury ◽

Neural Stem Progenitor Cells ◽

Stimulation Of

Download Full-text

Immunologic stimulation of early murine hematopoiesis and its abrogation by cyclosporin A

Blood ◽

10.1182/blood.v59.4.851.851 ◽

1982 ◽

Vol 59 (4) ◽

pp. 851-856 ◽

Cited By ~ 17

Author(s):

SA Burstein ◽

SK Erb ◽

JW Adamson ◽

LA Harker

Keyword(s):

Immune Response ◽

Cyclosporin A ◽

Progenitor Cells ◽

Pokeweed Mitogen ◽

Normal Rabbit Serum ◽

Lymphocyte Function ◽

Spleen Cells ◽

Stimulation Of

Abstract Mice injected chronically with antiplatelet serum develop an increase in the number of megakaryocytic progenitor cells compared to animals given normal rabbit serum. To examine the specificity of this response, progenitor cells giving rise to megakaryocyte, granulocyte-macrophage, erythroid, and mixed-cell colonies were assayed after injection of various heterosera or saline. All four colony types increased in the serum-treated groups. Since the in vitro proliferation of hematopoietic progenitor cells is promoted by supernatants of mitogen-stimulated spleen cells, we hypothesized that the immune response following antiserum administration resulted in the in vivo activation of T lymphocytes which produced or led to the production of colony stimulating activities. To test this hypothesis, cyclosporin A, a preferential inhibitor of T lymphocyte function, was given to mice concurrently with antiserum and also added to spleen cell cultures in the presence of pokeweed mitogen. Cyclosporin A abrogated the antiserum- related increases in progenitor cell numbers in vivo and the production of colony stimulating activity in vitro. The results suggest that the immune response related to antiserum administration results in the in vivo production of hematopoietic colony stimulating activities that may be identical to those produced in vitro by mitogen-stimulation of spleen cells.

Download Full-text