Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells

Susanna Tomasoni, Lorena Longaretti, Cinzia Rota, Marina Morigi, Sara Conti, Elisa Gotti, Chiara Capelli, Martino Introna, Giuseppe Remuzzi, Ariela Benigni

Research output: Contribution to journalArticle

Abstract

Bone marrow-mesenchymal stem cells (BM-MSC) ameliorate renal dysfunction and repair tubular damage of acute kidney injury by locally releasing growth factors, including the insulin-like growth factor-1 (IGF-1). The restricted homing of BM-MSC at the site of injury led us to investigate a possible gene-based communication mechanism between BM-MSC and tubular cells. Human BM-MSC (hBM-MSC) released microparticles and exosomes (Exo) enriched in mRNAs. A selected pattern of transcripts was detected in Exo versus parental cells. Exo expressed the IGF-1 receptor (IGF-1R), but not IGF-1 mRNA, while hBM-MSC contained both mRNAs. R- cells lacking IGF-1R exposed to hBM-MSC-derived Exo acquired the human IGF-1R transcript that was translated in the corresponding protein. Transfer of IGF-1R mRNA from Exo to cisplatin-damaged proximal tubular cells (proximal tubular epithelial cell [PTEC]) increased PTEC proliferation. Coincubation of damaged PTEC with Exo and soluble IGF-1 further enhanced cell proliferation. These findings suggest that horizontal transfer of the mRNA for IGF-1R to tubular cells through Exo potentiates tubular cell sensitivity to locally produced IGF-1 providing a new mechanism underlying the powerful renoprotection of few BM-MSC observed in vivo.

Original languageEnglish
Pages (from-to)772-780
Number of pages9
JournalStem Cells and Development
Volume22
Issue number5
DOIs
Publication statusPublished - Mar 1 2013

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

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