Cryopreservation of Network Bioactivity and Multi-Lineage Stromal Cell Differentiation Potential within Three-Dimensional Synthetic Hydrogels

2021 ◽  
Author(s):  
Sudhir Khetan
2021 ◽  
Vol 22 (8) ◽  
pp. 4011
Author(s):  
Brianna Chen ◽  
Dylan McCuaig-Walton ◽  
Sean Tan ◽  
Andrew P. Montgomery ◽  
Bryan W. Day ◽  
...  

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gayathri Subramanian ◽  
Alexander Stasuk ◽  
Mostafa Elsaadany ◽  
Eda Yildirim-Ayan

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.


Biomaterials ◽  
2013 ◽  
Vol 34 (10) ◽  
pp. 2389-2398 ◽  
Author(s):  
Wojtek Tutak ◽  
Sumona Sarkar ◽  
Sheng Lin-Gibson ◽  
Tanya M. Farooque ◽  
Giri Jyotsnendu ◽  
...  

2010 ◽  
Vol 82 (5) ◽  
pp. 1844-1850 ◽  
Author(s):  
Vishnu Vardhan Pully ◽  
Aufried Lenferink ◽  
Henk-Jan van Manen ◽  
Vinod Subramaniam ◽  
Clemens A. van Blitterswijk ◽  
...  

2013 ◽  
Vol 19 (9) ◽  
pp. 676-687 ◽  
Author(s):  
Hai Wang ◽  
Silvina Bocca ◽  
Sandra Anderson ◽  
Liang Yu ◽  
Bhaskara S. Rhavi ◽  
...  

2010 ◽  
Vol 16 (6) ◽  
pp. 1913-1923 ◽  
Author(s):  
John T. Connelly ◽  
Eric J. Vanderploeg ◽  
Janna K. Mouw ◽  
Christopher G. Wilson ◽  
Marc E. Levenston

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