The generation and use of human embryonic stem cells

Author(s):  
Mikael C. O. Englund ◽  
Christopher L. R. Barratt

Ever since the first human embryonic stem cells (hES) were successfully derived and propagated in 1998 (1), an obvious topic of discussion has been the development of novel therapies based on stem cell technology for a number of diseases and conditions. Targets could include type 1 diabetes, Alzheimer’s disease, spinal cord injury, and Parkinson’s disease to name a few. hES cells can also be used for tissue engineering, to replace for example bone and cartilage, and for drug discovery. Exciting proof of principal experiments in animals demonstrate the clinical potential in this field. For example, in a rat model of Parkinson’s disease, dopamine neural grafts derived from mouse Es cells showed long-term survival, the production of dopamine and, importantly, persistent improvements in movement behaviour (2). The promises of these potential treatments is enormous. However, there are many hurdles to overcome before a therapy based on stem cells is a clinical reality. We outline (A) the variety of methods to derive hES cells including somatic cell nuclear transfer (SCNT) and describe the challenges and possible avenues of further use; (B) discuss the development of clinical grade hES cells and their use in the drug discovery process; and (C) alternative strategies to patient specific therapy including induced adult pluripotent stem cells (iPS cells).

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Parinya Noisa ◽  
Taneli Raivio ◽  
Wei Cui

Human embryonic stem cells (hESCs) are able to proliferatein vitroindefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs). hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, includingNURR1, PITX3, andEN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.


2020 ◽  
Author(s):  
Aleksandra Filippova ◽  
Fabien Bonini ◽  
Liudmila Efremova ◽  
Olivier Preynat-Seauve ◽  
Amélie Béduer ◽  
...  

AbstractWe present in-vivo transplantation of mature dopaminergic neurons by means of macroporous, injectable carriers, to enhance cell therapy in Parkinson’s disease. The carriers are synthesized by crosslinking carboxymethylcellulose at subzero temperatures, resulting in cylindrical, highly resilient porous cryogels, which we term Neurothreads. We develop efficient covalent immobilization of the neural adhesion proteins laminin 111, collagen IV and fibronectin, as well as of the extracellular matrix extract Matrigel to the Neurothreads. We observe the highest neural spreading on laminin 111 and Matrigel. We show compatibility with established dopaminergic differentiation of both HS420 human embryonic stem cells and the LUHMES midbrain model cell line. The porous Neurothread carriers withstand compression during minimally invasive stereotactic injection, and ensure viability of mature neurons including extended neurites. Implanted into the striatum in mice, the Neurothreads enable survival of transplanted mature neurons obtained by directed differentiation of the HS420 human embryonic stem cells, as a dense tissue in situ, including dopaminergic cells. With the successful in-vivo transfer of intact, mature and fully open 3D neural networks, we provide a powerful tool to extend established differentiation protocols to higher maturity and to enhance preconfigured neural network transplantation.


Author(s):  
Catharina Ellerstrm ◽  
Petter Bjrquist ◽  
Peter Sartipy ◽  
Johan Hyllner ◽  
Raimund Strehl

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