title: Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise.
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.DQalpha1 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.
authors.affiliation: Foundation onlus Staminali e Vita, Institute of Biomedical Technologies, CNR, 56127 Pisa, Italy. rrevoltella@yahoo.it
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Revoltella
authors.forename: Sandra
authors.initials: S
authors.lastname: Papini
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rosellini
authors.forename: Monica
authors.initials: M
authors.lastname: Michelini
authors.forename: Valeria
authors.initials: V
authors.lastname: Franceschini
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciorba
authors.forename: Lucia
authors.initials: L
authors.lastname: Bertolaso
authors.forename: Sara
authors.initials: S
authors.lastname: Magosso
authors.forename: Stavros
authors.initials: S
authors.lastname: Hatzopoulos
authors.forename: Guiscardo
authors.initials: G
authors.lastname: Lorito
authors.forename: Pietro
authors.initials: P
authors.lastname: Giordano
authors.forename: Edi
authors.initials: E
authors.lastname: Simoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ognio
authors.forename: Michele
authors.initials: M
authors.lastname: Cilli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Serena
authors.initials: S
authors.lastname: Urbani
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jeffery
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martini
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D015703:Antigens, CD / Q000276:immunology*; D046528:Chimerism; D003051:Cochlea / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D003638:Deafness / Q000139:chemically induced / Q000473:pathology / Q000601:surgery; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006023:Glycoproteins / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007612:Kanamycin / Q000009:adverse effects*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009622:Noise / Q000009:adverse effects*; D010455:Peptides / Q000276:immunology*; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D007612:Kanamycin