scholarly journals Effects of Simulated Microgravity on Wild Type and Marfan hiPSCs-Derived Embryoid Bodies

Author(s):  
Paola Spitalieri ◽  
Mario Marini ◽  
Maria Giovanna Scioli ◽  
Michela Murdocca ◽  
Giuliana Longo ◽  
...  

Abstract Background Mechanical unloading in microgravity is thought to induce tissue degeneration by various mechanisms, including the inhibition of regenerative stem cell differentiation. In this work, we investigate the effects of microgravity simulation on early lineage commitment of hiPSCs from healthy and Marfan Syndrome (MFS; OMIM #154700) donors, using the embryoid bodies model of tissue differentiation and evaluating their ultra-structural conformation. MFS model involves an anomalous organization of the extracellular matrix for a deficit of fibrillin-1, an essential protein of connective tissue. Methods In vitro models require the use of embryoid bodies derived from hiPSCs. A DRPM was used to simulate microgravity conditions. Results Our data suggest an increase of the stemness of those EBs maintained in SMG condition. EBs are still capable of external migration, but are less likely to distinguish, providing a measure of the remaining progenitor or stem cell populations in the earlier stage. The microgravity response appears to vary between WT and Marfan EBs, presumably as a result of a cell structural component deficiency due to fibrillin-1 protein lack. In fact, MFS EBs show a reduced adaptive capacity to the environment of microgravity that prevented them from reacting and making rapid adjustments, while healthy EBs show stem retention, without any structural changes due to microgravity conditions. Conclusion EBs formation specifically mimics stem cell differentiation into embryonic tissues, this process has also significant similarities with adult stem cell-based tissue regeneration. The use of SMG devices for the maintenance of stem cells on regenerative medicine applications is becoming increasingly more feasible.

2009 ◽  
Vol 296 (1) ◽  
pp. H159-H170 ◽  
Author(s):  
Xiuju Li ◽  
Pratap Karki ◽  
Lei Lei ◽  
Huayan Wang ◽  
Larry Fliegel

Embryonic stem cells provide one potential source of cardiomyocytes for cardiac transplantation; however, after differentiation of stem cells in vitro, cardiomyocytes usually account for only a minority of cells present. To gain insights into improving cardiomyocyte development from stem cells, we examined the role of the Na+/H+ exchanger isoform 1 (NHE1) in cardiomyocyte differentiation. NHE1 protein and message levels were induced by treatment of CGR8 cells to form embryoid bodies and cardiomyocytes. The NHE1 protein was present on the cell surface and NHE1 inhibitor-sensitive activity was detected. Inhibition of NHE1 activity during differentiation of CGR8 cells prevented cardiomyocyte differentiation as indicated by decreased message for transcription factors Nkx2-5 and Tbx5 and decreased levels of α-myosin heavy chain protein. Increased expression of NHE1 from an adenoviral vector facilitated cardiomyocyte differentiation. Similar results were found with cardiomyocyte differentiation of P19 embryonal carcinoma cells. CGR8 cells were treated to induce differentiation, but when differentiation was inhibited by dispersing the EBs, myocardial development was inhibited. The results demonstrate that NHE1 activity is important in facilitating stem cell differentiation to cardiomyocyte lineage. Elevated NHE1 expression appears to be triggered as part of the process that facilitates cardiomyocyte development.


2011 ◽  
Vol 31 (8) ◽  
pp. 1842-1852 ◽  
Author(s):  
Qingzhong Xiao ◽  
Gang Wang ◽  
Xiaoke Yin ◽  
Zhenling Luo ◽  
Andriani Margariti ◽  
...  

2017 ◽  
Vol 8 (1) ◽  
pp. e2568-e2568 ◽  
Author(s):  
Francesca Paino ◽  
Marcella La Noce ◽  
Diego Di Nucci ◽  
Giovanni Francesco Nicoletti ◽  
Rosa Salzillo ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Quyen A. Tran ◽  
Visar Ajeti ◽  
Brian T. Freeman ◽  
Paul J. Campagnola ◽  
Brenda M. Ogle

Developmental studies and 3D in vitro model systems show that the production and engagement of extracellular matrix (ECM) often precede stem cell differentiation. Yet, unclear is how the ECM triggers signaling events in sequence to accommodate multistep process characteristic of differentiation. Here, we employ transcriptome profiling and advanced imaging to delineate the specificity of ECM engagement to particular differentiation pathways and to determine whether specificity in this context is a function of long-term ECM remodeling. To this end, human mesenchymal stem cells (hMSCs) were cultured in 3D bioprinted prisms created from ECM proteins and associated controls. We found that exogenous ECM provided in 3D microenvironments at early time points impacts on the composition of microenvironments at later time points and that each evolving 3D microenvironment is uniquely poised to promote stem cell differentiation. Moreover, 2D cultures undergo minimal ECM remodeling and are ill-equipped to stimulate pathways associated with development.


2020 ◽  
Vol 105 ◽  
pp. 203-213 ◽  
Author(s):  
Yangzi Isabel Tian ◽  
Xulang Zhang ◽  
Karen Torrejon ◽  
John Danias ◽  
Sofya Gindina ◽  
...  

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