Graduate Student Oral Presentation 2
Metabolic Reprograming during Non-adherent Culture Selects
Primitive Human Mesenchymal Stem Cells
Yijun Liu1, Ang-Chen Tsai1, Teng Ma1
1
Chemical and Biomedical, Florida State University
Abstract
Removal of human mesenchymal stem cells (hMSCs) from in vivo niche for in vitro bioprocessing in an
artificial culture environment induces senescence that reduce hMSC potency and impede translation of hMSC
to clinical application1. Recent studies on the non-adherent culture of anchorage-dependent cells suggest the
strong correlation between self-assembled aggregates and cellular ‘stemmess’, and indeed aggregates of
hMSCs exhibit enhanced pluripotent stem cells genes expression and primitive stem cells functions. Although
it has been suggested that in vitro aggregation mimics mesenchymal condensation and recapitulates the
cellular events of in vivo microenvironment, the molecular link between aggregation and hMSCs stemness is
still undefined. In the present study, we test the hypotheses that hMSC aggregation on non-adherent
substratum initiates mitochondrial remodeling and metabolism reconfiguration, resulting in a metabolic
profile that resembles primitive stem cells. Our results show that aggregation of hMSCs influences
mitochondrial dynamics and results in a reduction in mitochondrial function. Adaptive changes as a result of
mitochondrial dysfunction includes increased glycolytic and anaplerotic flux, which fuel the self-digestion
program named autophagy. Importantly, we identify that alteration of mitochondrial respiration chain is
responsible for the enhanced expression of stem cell genes because treatment of respiration chain targeted
small molecules partially recapitulates stemness enhancement event in planar culture. Our finding
demonstrates that mitochondria play significant role in stem cell pluripotency by its retrograde signaling with
stem cell gene expression program (Fig.1).
Reference
2.
Ma T, Tsai A, Liu Y. 2015. Biomanufacturing of Human Mesenchymal
Stem Cells in Cell Therapy: Influence of Microenvironment on Scalable
Expansion in Bioreactors. Biochemical Engineering Journal. 108: 44.
Fig.1 Mitochondrial retrograde signaling in hMSCs aggregates.
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