Cell Transplantation (Jun 2008)

Cochlear Repair by Transplantation of Human Cord Blood CD133+ Cells to Nod-Scid Mice Made Deaf with Kanamycin and Noise

  • Roberto P. Revoltella M.D., Ph.D.,
  • 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

DOI
https://doi.org/10.3727/096368908786092685
Journal volume & issue
Vol. 17

Abstract

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We investigated the fate of human cord blood CD133+ hematopoietic stem cells (HSC) transplanted intravenously (IV) into irradiated nodscid 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.