Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise

Roberto P. Revoltella, Sandra Papini, Alfredo Rosellini, Monica Michelini, Valeria Franceschini, Andrea Ciorba, Lucia Bertolaso, Sara Magosso, Stavros Hatzopoulos, Guiscardo Lorito, Pietro Giordano, Edi Simoni, Emanuela Ognio, Michele Cilli, Riccardo Saccardi, Serena Urbani, Rosemary Jeffery, Richard Poulsom, Alessandro Martini

Research output: Contribution to journalArticle

Abstract

We investigated the fate of human cord blood CD133+ hematopoietic stem cells (HSC) transplanted intravenously (IV) into irradiated nod-scid mice previously made deaf by ototoxic treatment with kanamycin and/or intense noise, to verify whether HSC engraft the cochlea and contribute to inner ear restoration, in vivo. We tested the presence of HLA.DQα1 by PCR, used for traceability of engrafted cells, finding evidence that HSC migrated to various host tissues, including the organ of Corti (OC). By histology, antibody and lectin-staining analysis, we confirmed that HSC IV transplantation in mice previously damaged by ototoxic agents correlated with the repair process and stimulation ex novo of morphological recovery in the inner ear, while the cochlea of control oto-injured, nontransplanted mice remained seriously damaged. Dual color FISH analysis also provided evidence of positive engraftment in the inner ear and in various mouse tissues, also revealing small numbers of heterokaryons, probably derived from fusion of donor with endogenous cells, for up to 2 months following transplantation. These observations offer the first evidence that transplanted human HSC migrating to the inner ear of oto-injured mice may provide conditions for the resumption of deafened cochlea, emerging as a potential strategy for inner ear rehabilitation.

Original languageEnglish
Pages (from-to)665-678
Number of pages14
JournalCell Transplantation
Volume17
Issue number6
DOIs
Publication statusPublished - 2008

Keywords

  • Cochlea repair
  • Deafness
  • Organ of corti
  • Stem cell
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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