scholarly journals Using Small Molecules to Great Effect in Stem Cell Differentiation

2009 ◽  
Vol 4 (5) ◽  
pp. 373-374 ◽  
Author(s):  
Kenneth S. Zaret
Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 192
Author(s):  
Pietro Marchese ◽  
Nipun Mahajan ◽  
Enda O’Connell ◽  
Howard Fearnhead ◽  
Maria Tuohy ◽  
...  

Worldwide diffused diseases such as osteoarthritis, atherosclerosis or chronic kidney disease are associated with a tissue calcification process which may involve unexpected local stem cell differentiation. Current pharmacological treatments for such musculoskeletal conditions are weakly effective, sometimes extremely expensive and often absent. The potential to develop new therapies is represented by the discovery of small molecules modulating resident progenitor cell differentiation to prevent aberrant tissue calcification. The marine environment is a rich reserve of compounds with pharmaceutical potential and many novel molecules are isolated from macro and microorganisms annually. The potential of small molecules synthetized by marine filamentous fungi to influence the osteogenic and chondrogenic differentiation of human mesenchymal stem/stromal cells (hMSCs) was investigated using a novel, high-throughput automated screening platform. Metabolites synthetized by the marine-derived fungus Penicillium antarcticum were evaluated on the platform. Itaconic acid derivatives were identified as inhibitors of calcium elaboration into the matrix of osteogenically differentiated hMSCs and also inhibited hMSC chondrogenic differentiation, highlighting their capacity to impair ectopic calcification. Bioactive small molecule discovery is critical to address ectopic tissue calcification and the use of biologically relevant assays to identify naturally occurring metabolites from marine sources represents a strategy that can contribute to this effort.


2021 ◽  
Author(s):  
Gherman Novakovsky ◽  
Shugo Sasaki ◽  
Oriol Fornes ◽  
Meltem E. Omur ◽  
Helen Huang ◽  
...  

Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by including this compound achieves the same differentiation efficiency with a 90% cost reduction. The gene expression profile induced by the compound suggests that it is an inhibitor of the MYC pathway. The proposed in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols.


2016 ◽  
Vol 34 (4) ◽  
pp. 250-261 ◽  
Author(s):  
Leila Soltani ◽  
Hamid Reza Rahmani ◽  
Morteza Daliri Joupari ◽  
Hori Ghaneialvar ◽  
Amir Hossein Mahdavi ◽  
...  

2013 ◽  
Vol 135 (42) ◽  
pp. 15682-15685 ◽  
Author(s):  
Shreyas Shah ◽  
Aniruddh Solanki ◽  
Pijus K. Sasmal ◽  
Ki-Bum Lee

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