Student Oral Presentation #3
Mechanism and Metabolic Control of Mesenchymal Stem Cell
In vitro Aging
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Xuegang Yuan 1 , Yijun Liu 1 , Angchen Tsai 1 , and Teng Ma 1
Chemical and Biomedical Engineering, The Florida State University, Tallahassee FL
Abstract
Human mesenchymal stem cells (hMSCs) have emerged as an important cell source for stem cell therapy
because of their properties: self-renewal, multi-linage differentiation, paracrine effect and immunomodulation.
Clinical application requires allogenic and culture-expanded hMSCs with defined property and large scale
production. However, in vitro culture-expansion of hMSCs leads to cell senescence and decrease of therapeutic
potency, which is a major barrier for hMSCs based therapeutic application. Results from previous studies
demonstrate that long-term culture of hMSCs results in phenotype change and metabolic shift from aerobic
glycolysis towards oxidative phosphorylation (OXPHOS), leading cell to an in vitro aging state after rapid
culture expansion 1 .
In this work, we studied the metabolic reconfiguration of long-term cultured hMSCs at high passage to
investigate the mechanism of metabolic shift and phenotype change. High passage hMSCs have increased
mitochondria mass, reduced mitochondria membrane potential and autophagy compare to early passage hMSCs.
Characterization of energy pathway and metabolic profile of high passage hMSCs showed the shift of
metabolism to OXPHOS to support rapid proliferation rate, which contributes to the accumulation of cytotoxic
metabolic byproducts. Engineering methods of maintaining or re-establishing culture-expanded hMSCs
phenotype and cellular homestasis could be applied to maintain or re-estab