scholarly journals Emerging Opportunities in Human Pluripotent Stem-Cells Based Assays to Explore the Diversity of Botulinum Neurotoxins as Future Therapeutics

2021 ◽  
Vol 22 (14) ◽  
pp. 7524
Author(s):  
Juliette Duchesne de Lamotte ◽  
Anselme Perrier ◽  
Cécile Martinat ◽  
Camille Nicoleau
Keyword(s):  
Stem Cells ◽  
Human Physiology ◽  
Nervous System ◽  
Pluripotent Stem Cells ◽  
Clostridium Botulinum ◽  
Food Poisoning ◽  
Cost Effective ◽  
Human Pluripotent Stem Cells ◽  
Neuronal Function ◽  
Botulinum Neurotoxins

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and are responsible for botulism, a fatal disorder of the nervous system mostly induced by food poisoning. Despite being one of the most potent families of poisonous substances, BoNTs are used for both aesthetic and therapeutic indications from cosmetic reduction of wrinkles to treatment of movement disorders. The increasing understanding of the biology of BoNTs and the availability of distinct toxin serotypes and subtypes offer the prospect of expanding the range of indications for these toxins. Engineering of BoNTs is considered to provide a new avenue for improving safety and clinical benefit from these neurotoxins. Robust, high-throughput, and cost-effective assays for BoNTs activity, yet highly relevant to the human physiology, have become indispensable for a successful translation of engineered BoNTs to the clinic. This review presents an emerging family of cell-based assays that take advantage of newly developed human pluripotent stem cells and neuronal function analyses technologies.

scholarly journals Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy

2021 ◽  
Author(s):  
Tingcai Pan ◽  
Ning Wang ◽  
Jiaye Zhang ◽  
Fan Yang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Small Molecules ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Cost Effective ◽  
Human Pluripotent Stem Cells ◽  
Scale Production ◽  
Hepatic Cells ◽  
Cell Based Therapy

Abstract Background: Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable. Methods: We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.Results: We demonstrated that small-molecule cocktail CIP efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo. Conclusion: Our current small-molecule based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.

scholarly journals Prospect of Human Pluripotent Stem Cell-Derived Neural Crest Stem Cells in Clinical Application

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Qian Zhu ◽  
Qiqi Lu ◽  
Rong Gao ◽  
Tong Cao
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Crest ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Hirschsprung Disease ◽  
Cell Types ◽  
Human Pluripotent Stem Cells ◽  
Neural Crest Stem Cells

Neural crest stem cells (NCSCs) represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration.

scholarly journals A chemical tool for improved culture of human pluripotent stem cells

2020 ◽  
Author(s):  
Laurence Silpa ◽  
Maximilian Schuessler ◽  
Gu Liu ◽  
Marcus Olivecrona ◽  
Lucia Groizard-Payeras ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
3D Culture ◽  
Cost Effective ◽  
Human Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Kinase C ◽  
2D And 3D ◽  
Cell Cell

AbstractThe large-scale and cost-effective production of quality-controlled human pluripotent stem cells (hPSC) for use in cell therapy and drug discovery requires chemically-defined xenobiotic-free culture systems that enable easy and homogeneous expansion of pluripotent cells. Through phenotypic screening, we have identified a small molecule, OXS8360 (an optimized derivative of (-)-Indolactam V ((-)-ILV)), that stably disrupts hPSC cell-cell contacts. Proliferation of hPSC in OXS8360 is normal, as are pluripotency signatures, directed differentiation to hallmark lineages and karyotype over extended passaging. In 3D culture, OXS8360-treated hPSC form smaller, more uniform aggregates, that are easier to dissociate, greatly facilitating expansion. The mode of action of OXS8360 involves disruption of the localisation of the cell-cell adhesion molecule E-cadherin, via activation of unconventional Protein Kinase C isoforms. OXS8360 media supplementation is therefore able to yield more uniform, disaggregated 2D and 3D hPSC cultures, providing the hPSC field with an affordable tool to improve hPSC quality and scalability.

Human Pluripotent Stem Cells and Drug Discovery: A New Beginning

2016 ◽  
Vol 1 (1) ◽  
pp. 27
Author(s):  
Vinod Verma ◽  
A. Mehta ◽  
S.J.S. Flora
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Pluripotent Stem Cells ◽  
Cost Effective ◽  
Cell Types ◽  
In Vitro Models ◽  
Human Pluripotent Stem Cells ◽  
Specific Cell ◽  
Attrition Rates

Human pluripotent stem cells (hPSCs) offer unique opportunities to discover and develop a new generation of drugs. Their ability to differentiate into virtually any cell type renders them a cost-effective, renewable source of tissue-specific cell types capable of predicting human responses towards novel chemical entities. Using these improved in vitro models based on physiologically relevant human cell types could result in identifying highly precise and safe compounds, thereby reducing drug attrition rates. Moreover, ability to develop humanised disease models for patient-stratified drug screening makes hPSCs an impeccable tool in translational medicine. In this mini-review we focus on the positives and negatives of utilising hPSC-derived cell types as drug discovery platforms with special emphasis on cardio-, hepato- and embryotoxicity.

Advanced Modeling of Peripheral Neuro-Effector Communication and -Plasticity

Physiology ◽  
2020 ◽  
Vol 35 (5) ◽  
pp. 348-357 ◽  
Author(s):  
Pien A. Goldsteen ◽  
Amalia M. Dolga ◽  
Reinoud Gosens
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Great Promise ◽  
Organ On A Chip ◽  
Organoid Cultures

The peripheral nervous system (PNS) plays crucial roles in physiology and disease. Neuro-effector communication and neuroplasticity of the PNS are poorly studied, since suitable models are lacking. The emergence of human pluripotent stem cells (hPSCs) has great promise to resolve this deficit. hPSC-derived PNS neurons, integrated into organ-on-a-chip systems or organoid cultures, allow co-cultures with cells of the local microenvironment to study neuro-effector interactions and to probe mechanisms underlying neuroplasticity.

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