bims-mireme Biomed News
on Mitochondria in regenerative medicine
Issue of 2021‒03‒07
nine papers selected by
Brian Spurlock
University of Alabama at Birmingham

  1. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(21)00061-8. [Epub ahead of print]28(3): 394-408
      Recent evidence supports the notion that mitochondrial metabolism is necessary for the determination of stem cell fate. Historically, mitochondrial metabolism is linked to the production of ATP and tricarboxylic acid (TCA) cycle metabolites to support stem cell survival and growth, respectively. However, it is now clear that beyond these canonical roles, mitochondria as signaling organelles dictate stem cell fate and function. In this review, we focus on key conceptual ideas on how mitochondria control mammalian stem cell fate and function through reactive oxygen species (ROS) generation, TCA cycle metabolite production, NAD+/NADH ratio regulation, pyruvate metabolism, and mitochondrial dynamics.
    Keywords:  L-2-HG; ROS; TCA cycle; acetyl-CoA; epigenetics; mitochondrial dynamics; pyruvate
  2. Front Genet. 2021 ;12 632810
      The use of differentiating human induced pluripotent stem cells (hiPSCs) in mini-tissue organoids provides an invaluable resource for regenerative medicine applications, particularly in the field of disease modeling. However, most studies using a kidney organoid model, focused solely on the transcriptomics and did not explore mechanisms of regulating kidney organoids related to metabolic effects and maturational phenotype. Here, we applied metabolomics coupled with transcriptomics to investigate the metabolic dynamics and function during kidney organoid differentiation. Not only did we validate the dominant metabolic alteration from glycolysis to oxidative phosphorylation in the iPSC differentiation process but we also showed that glycine, serine, and threonine metabolism had a regulatory role during kidney organoid formation and lineage maturation. Notably, serine had a role in regulating S-adenosylmethionine (SAM) to facilitate kidney organoid formation by altering DNA methylation. Our data revealed that analysis of metabolic characterization broadens our ability to understand phenotype regulation. The utilization of this comparative omics approach, in studying kidney organoid formation, can aid in deciphering unique knowledge about the biological and physiological processes involved in organoid-based disease modeling or drug screening.
    Keywords:  induced pluripotent stem cells; kidney organoids; metabolomics; serine metabolism; transcriptomics
  3. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(21)00066-7. [Epub ahead of print]28(3): 409-423
      The expanding field of stem cell metabolism has been supported by technical advances in metabolite profiling and novel functional analyses. While use of these methodologies has been fruitful, many challenges are posed by the intricacies of culturing stem cells in vitro, along with the distinctive scarcity of adult tissue stem cells and the complexities of their niches in vivo. This review provides an examination of the methodologies used to characterize stem cell metabolism, highlighting their utility while placing a sharper focus on their limitations and hurdles the field needs to overcome for the optimal study of stem cell metabolic networks.
  4. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(21)00067-9. [Epub ahead of print]28(3): 374-377
      The depth of quiescence in hematopoietic stem cells (HSCs) dictates their potency and is sensitive to metabolic perturbations. Recent evidence suggests that lysosomal functions distinct from autophagic processes are pivotal in regulating quiescence versus activation by potential control of the access to a nutrient reservoir required for HSC activation.
  5. Biochim Biophys Acta Rev Cancer. 2021 Feb 25. pii: S0304-419X(21)00026-3. [Epub ahead of print] 188527
      An improved understanding of stem cell niches, organogenesis, and disease models has paved the way for developing a three-dimensional (3D) organoid culture system. Organoid cultures can be derived from primary tissues (single cells or tissue subunits), induced pluripotent stem cells (iPSCs), or embryonic stem cells (ESCs). As a significant technological breakthrough, 3D organoid models offer a promising approach for understanding the complexities of human diseases ranging from the mechanistic investigation of disease pathogenesis to therapy. Here, we discuss the recent applications, advantages, and limitations of organoids as in vitro models for studying metabolomics, drug development, infectious diseases, and the gut microbiome. We further discuss the use of organoids in cancer modeling using high throughput sequencing approaches.
    Keywords:  Disease modeling; Gut MIcrobiota; Metabolism; Organoids; Tumor microenvironment
  6. Int J Mol Sci. 2021 Feb 12. pii: 1824. [Epub ahead of print]22(4):
      With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the "stem- less" approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.
    Keywords:  aging; cardiovascular; heart; mitochondria; senescence; stem cell; transplantation