scholarly journals Three-dimensional induction of dorsal, intermediate and ventral spinal cord tissues from human pluripotent stem cells

Development ◽  
2018 ◽  
Vol 145 (16) ◽  
pp. dev162214 ◽  
Author(s):  
Takenori Ogura ◽  
Hideya Sakaguchi ◽  
Susumu Miyamoto ◽  
Jun Takahashi
2021 ◽  
Author(s):  
Philippe J.R. Cohen ◽  
Elisa Luquet ◽  
Justine Pletenka ◽  
Andrea Leonard ◽  
Elise Warter ◽  
...  

Human pluripotent stem cells (hPSCs) have emerged as the most promising cellular source for cell therapies. To overcome scale up limitations of classical 2D culture systems, suspension cultures have been developed to meet the need of large-scale culture in regenerative medicine. Despite constant improvements, current protocols relying on the generation of micro-carriers or cell aggregates only achieve moderate amplification performance. Here, guided by reports showing that hPSCs can self-organize in vitro into cysts reminiscent of the epiblast stage in embryo development, we developed a physio-mimetic approach for hPSC culture. We engineered stem cell niche microenvironments inside microfluidics-assisted core-shell microcapsules. We demonstrate that lumenized three-dimensional colonies maximize viability and expansion rates while maintaining pluripotency. By optimizing capsule size and culture conditions, we scale-up this method to industrial scale stirred tank bioreactors and achieve an unprecedented hPSC amplification rate of 282-fold in 6.5 days.


Development ◽  
2017 ◽  
Vol 144 (6) ◽  
pp. 1008-1017 ◽  
Author(s):  
Elisa Giacomelli ◽  
Milena Bellin ◽  
Luca Sala ◽  
Berend J. van Meer ◽  
Leon G. J. Tertoolen ◽  
...  

2017 ◽  
Vol 49 (7) ◽  
pp. e361-e361 ◽  
Author(s):  
Dae-Sung Kim ◽  
Se Jung Jung ◽  
Jae Souk Lee ◽  
Bo Young Lim ◽  
Hyun Ah Kim ◽  
...  

2017 ◽  
Vol 114 (19) ◽  
pp. 4969-4974 ◽  
Author(s):  
Jessica C. Butts ◽  
Dylan A. McCreedy ◽  
Jorge Alexis Martinez-Vargas ◽  
Frederico N. Mendoza-Camacho ◽  
Tracy A. Hookway ◽  
...  

The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10+ V2a interneurons from human pluripotent stem cells (hPSCs). Signaling pathways (retinoic acid, sonic hedgehog, and Notch) that pattern the neural tube were sequentially perturbed to identify an optimized combination of small molecules that yielded ∼25% CHX10+ cells in four hPSC lines. Differentiated cultures expressed much higher levels of V2a phenotypic markers (CHX10 and SOX14) than other neural lineage markers. Over time, CHX10+ cells expressed neuronal markers [neurofilament, NeuN, and vesicular glutamate transporter 2 (VGlut2)], and cultures exhibited increased action potential frequency. Single-cell RNAseq analysis confirmed CHX10+ cells within the differentiated population, which consisted primarily of neurons with some glial and neural progenitor cells. At 2 wk after transplantation into the spinal cord of mice, hPSC-derived V2a cultures survived at the site of injection, coexpressed NeuN and VGlut2, extended neurites >5 mm, and formed putative synapses with host neurons. These results provide a description of V2a interneurons differentiated from hPSCs that may be used to model central nervous system development and serve as a potential cell therapy for SCI.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yan-Ru Lou ◽  
Liisa Kanninen ◽  
Bryan Kaehr ◽  
Jason L. Townson ◽  
Johanna Niklander ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document