Pluripotent stem cell energy metabolism: an update

TeSlaa, Tara; Teitell, Michael A.

doi:10.15252/embj.201490446

Cited by 195 publications

(190 citation statements)

References 208 publications

(247 reference statements)

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“…Recent data support strong and direct involvement of mitochondria and oxidative metabolism in the regulation of stem cell pluripotency [3]. Cells adapt the number and activity of mitochondria in response to environmental and cellular cues through biogenesis, turnover, and fusion and fission processes [4].…”

Section: Introductionmentioning

confidence: 92%

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Connecting Mitochondria, Metabolism, and Stem Cell Fate

Wanet

Arnould

Najimi

et al. 2015

Stem Cells and Development

260

216

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As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases.

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Section: Introductionmentioning

confidence: 92%

“…Emerging evidence also points toward a role for mitochondrial fusion and fission in signaling pathways regulating stem cell proliferation and differentiation [3]. Mitochondrial elongation requires the fusion of the outer and inner mitochondrial membranes (OMM and IMM).…”

Section: A New Shape For a New Fate: Mitochondrial Dynamics As A Regumentioning

confidence: 99%

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Wanet

Arnould

Najimi

et al. 2015

Stem Cells and Development

260

216

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“…Energy metabolism plays a highly important role for maintaining pluripotency of pluripotent stem cells and their further differentiation (Harvey et al, 2016;Teslaa & Teitell, 2015). Therefore, monitoring metabolites such as glucose and lactate should be performed throughout the culture process.…”

Section: Quantification Of Spinner and Bioreactor Aggregatesmentioning

confidence: 99%

Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single‐use bioreactors

Kwok

Ueda

Kadari

et al. 2017

J Tissue Eng Regen Med

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The production of human induced pluripotent stem cells (hiPSCs) in quantities that are relevant for cell-based therapies and cell-loaded implants through standard adherent culture is hardly achievable and lacks process scalability. A promising approach to overcoming these hurdles is the culture of hiPSCs in suspension. In this study, stirred suspension culture vessels were investigated for their suitability in the expansion of two hiPSC lines inoculated as a single cell suspension, with a free scalability between volumes of 50 and 2400 ml. The simple and robust two-step process reported here first generates hiPSC aggregates of 324 ± 71 μm diameter in 7 days in 125 ml spinner flasks (100 ml volume). These are subsequently dissociated into a single cell suspension for inoculation in 3000 ml bioreactors (1000 ml volume), finally yielding hiPSC aggregates of 198 ± 58 μm after 7 additional days. In both spinner flasks and bioreactors, hiPSCs can be cultured as aggregates for more than 40 days in suspension, maintain an undifferentiated state as confirmed by the expression of pluripotency markers TRA-1-60, TRA-1-81, SSEA-4, OCT4, and SOX2, can differentiate into cells of all three germ layers, and can be directed to differentiate into specific lineages such as cardiomyocytes. Up to a 16-fold increase in hiPSC quantity at the 100 ml volume was achieved, corresponding to a fold increase per day of 2.28; at the 1000 ml scale, an additional 10-fold increase was achieved. Taken together, 16 × 10 6 hiPSCs were expanded into 2 × 10 9 hiPSCs in 14 days for a fold increase per day of 8.93. This quantity of hiPSCs readily meets the requirements of cell-based therapies and brings their clinical potential closer to fruition.

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“…A key feature of the naïve state in the mouse is an enhanced capacity for oxidative phosphorylation, along with more active mitochondria, in contrast to EpiSCs, which rely more on glycolysis and have less-developed mitochondria (Teslaa and Teitell, 2015). Thus, mESCs can achieve both oxidative phosphorylation and glycolysis.…”

Section: Assaying the Pluripotent State In Vitromentioning

confidence: 99%

The pluripotent state in mouse and human

2015

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In the mouse, naïve pluripotent stem cells (PSCs) are thought to represent the cell culture equivalent of the late epiblast in the preimplantation embryo, with which they share a unique defining set of features. Recent studies have focused on the identification and propagation of a similar cell state in human. Although the capture of an exact human equivalent of the mouse naïve PSC remains an elusive goal, comparative studies spurred on by this quest are lighting the path to a deeper understanding of pluripotent state regulation in early mammalian development.

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Pluripotent stem cell energy metabolism: an update

Cited by 195 publications

References 208 publications

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single‐use bioreactors

The pluripotent state in mouse and human

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