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Human mesenchymal stromal cells transplanted into mice stimulate renal tubular cells and enhance mitochondrial function

Author

Listed:
  • Luca Perico

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Marina Morigi

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Cinzia Rota

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Matteo Breno

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Caterina Mele

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Marina Noris

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Martino Introna

    (Laboratory of Cell Therapy “G. Lanzani”, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII)

  • Chiara Capelli

    (Laboratory of Cell Therapy “G. Lanzani”, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII)

  • Lorena Longaretti

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Daniela Rottoli

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Sara Conti

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Daniela Corna

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

  • Giuseppe Remuzzi

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri
    Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII
    University of Milan)

  • Ariela Benigni

    (IRCCS—Istituto di Ricerche Farmacologiche Mario Negri)

Abstract

Mesenchymal stromal cells (MSCs) are renoprotective and drive regeneration following injury, although cellular targets of such an effect are still ill-defined. Here, we show that human umbilical cord (UC)-MSCs transplanted into mice stimulate tubular cells to regain mitochondrial mass and function, associated with enhanced microtubule-rich projections that appear to mediate mitochondrial trafficking to create a reparative dialogue among adjacent tubular cells. Treatment with UC-MSCs in mice with cisplatin-induced acute kidney injury (AKI) regulates mitochondrial biogenesis in proximal tubuli by enhancing PGC1α expression, NAD+ biosynthesis and Sirtuin 3 (SIRT3) activity, thus fostering antioxidant defenses and ATP production. The functional role of SIRT3 in tubular recovery is highlighted by data that in SIRT3-deficient mice with AKI, UC-MSC treatment fails to induce renoprotection. These data document a previously unrecognized mechanism through which UC-MSCs facilitate renal repair, so as to induce global metabolic reprogramming of damaged tubular cells to sustain energy supply.

Suggested Citation

  • Luca Perico & Marina Morigi & Cinzia Rota & Matteo Breno & Caterina Mele & Marina Noris & Martino Introna & Chiara Capelli & Lorena Longaretti & Daniela Rottoli & Sara Conti & Daniela Corna & Giuseppe, 2017. "Human mesenchymal stromal cells transplanted into mice stimulate renal tubular cells and enhance mitochondrial function," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00937-2
    DOI: 10.1038/s41467-017-00937-2
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