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Mesenchymal stem cells from preterm to term newborns undergo a significant switch from anaerobic glycolysis to the oxidative phosphorylation

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Abstract

We evaluated the energy metabolism of human mesenchymal stem cells (MSC) isolated from umbilical cord (UC) of preterm (< 37 weeks of gestational age) and term (≥ 37 weeks of gestational age) newborns, using MSC from adult bone marrow as control. A metabolic switch has been observed around the 34th week of gestational age from a prevalently anaerobic glycolysis to the oxidative phosphorylation. This metabolic change is associated with the organization of mitochondria reticulum: preterm MSCs presented a scarcely organized mitochondrial reticulum and low expression of proteins involved in the mitochondrial fission/fusion, compared to term MSCs. These changes seem governed by the expression of CLUH, a cytosolic messenger RNA-binding protein involved in the mitochondria biogenesis and distribution inside the cell; in fact, CLUH silencing in term MSC determined a metabolic fingerprint similar to that of preterm MSC. Our study discloses novel information on the production of energy and mitochondrial organization and function, during the passage from fetal to adult life, providing useful information for the management of preterm birth.

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Acknowledgements

This work was supported by funds from Cinque per mille e Ricerca Corrente, Ministero della Salute, to Istituto Giannina Gaslini; a Compagnia di San Paolo Grant (2014AAI637.U/812/AR pv 2013.0958 to F.F) and a Grant FIRB (2012# RBFR1299K0_002 to C.F.). The authors are indebted to Dr. Federica Raggi for providing the hypoxia incubator.

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Authors and Affiliations

  1. Stem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy

    Silvia Ravera, Marina Podestà, Federica Sabatini & Francesco Frassoni

  2. Section of Biochemistry, Department of Experimental Medicine, University of Genoa, 16132, Genoa, Italy

    Chiara Fresia

  3. SC Laboratory of Musculoskeletal Cell Biology, IRCCS Rizzoli Orthopedic Institute, 40136, Bologna, Italy

    Marta Columbaro

  4. Section of Human Anatomy, Department of Experimental Medicine, University of Genoa, 16132, Genoa, Italy

    Silvia Bruno

  5. Laboratory Medicine and Diagnostic Services, Division of Perinatal Pathology, Department of Translational Research, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy

    Ezio Fulcheri

  6. Neonatal Intensive Care Unit, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy

    Luca Antonio Ramenghi

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  1. Silvia Ravera
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  2. Marina Podestà
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Correspondence to Silvia Ravera.

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18_2017_2665_MOESM1_ESM.tif

Supplementary material 1 Suppl Figure 1 Phenotypical characterization of UC-MSC from preterm and term neonates. Phenotypical characterization of UC-MSC from preterm and term neonates. Panel a shows histograms of flow cytometry analyses demonstrating the expression of surface molecules of preterm MSC (preterm) compared with term MSC (term) and normal bone marrow-derived MSC (NBM). b Reports a representative flow cytometric analysis of Nestin, OCT3/4, NANOG, and SSEA-4 expression by preterm and term MSC. The gray histograms show the region of fluorescent intensity of the specific antibody and bold empty histograms represent staining of respective isotype-matched control immunoglobulins. Values are represented as percentage (%) of positive cells (TIFF 10330 kb)

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Ravera, S., Podestà, M., Sabatini, F. et al. Mesenchymal stem cells from preterm to term newborns undergo a significant switch from anaerobic glycolysis to the oxidative phosphorylation. Cell. Mol. Life Sci. 75, 889–903 (2018). https://doi.org/10.1007/s00018-017-2665-z

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  • DOI: https://doi.org/10.1007/s00018-017-2665-z

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