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

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 Remuzzi and Ariela Benigni
Additional contact information
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
Ariela Benigni: IRCCS—Istituto di Ricerche Farmacologiche Mario Negri

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00937-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00937-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00937-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().