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

模拟微重力对野生型和马凡型 hiPSC 衍生胚状体的影响

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作者:Paola Spitalieri, Mario Marini, Maria Giovanna Scioli, Michela Murdocca, Giuliana Longo, Augusto Orlandi, Giuseppe Novelli, Federica Sangiuolo

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.

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.

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.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12195-021-00680-1.

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