Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils

2004 ◽  
Vol 78 (2) ◽  
pp. 215-223 ◽  
Author(s):  
Satoru Ishibashi ◽  
Masanori Sakaguchi ◽  
Toshihiko Kuroiwa ◽  
Mami Yamasaki ◽  
Yonehiro Kanemura ◽  
...  
2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  

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.


2011 ◽  
Vol 4 (1) ◽  
pp. 35 ◽  
Author(s):  
Junichi Yamane ◽  
Satoru Ishibashi ◽  
Masanori Sakaguchi ◽  
Toshihiko Kuroiwa ◽  
Yonehiro Kanemura ◽  
...  

Cell Reports ◽  
2021 ◽  
Vol 37 (8) ◽  
pp. 110019
Author(s):  
Momotaro Kawai ◽  
Kent Imaizumi ◽  
Mitsuru Ishikawa ◽  
Shinsuke Shibata ◽  
Munehisa Shinozaki ◽  
...  

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Brenda Gutierrez ◽  
Lisa A Flanagan

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.


PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76860 ◽  
Author(s):  
Taesup Cho ◽  
Jae K. Ryu ◽  
Changiz Taghibiglou ◽  
Yuan Ge ◽  
Allen W. Chan ◽  
...  

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