Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise.
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.
Revoltella
Roberto P
RP
Foundation onlus Staminali e Vita, Institute of Biomedical Technologies, CNR, 56127 Pisa, Italy. rrevoltella@yahoo.it
Papini
Sandra
S
Rosellini
Alfredo
A
Michelini
Monica
M
Franceschini
Valeria
V
Ciorba
Andrea
A
Bertolaso
Lucia
L
Magosso
Sara
S
Hatzopoulos
Stavros
S
Lorito
Guiscardo
G
Giordano
Pietro
P
Simoni
Edi
E
Ognio
Emanuela
E
Cilli
Michele
M
Saccardi
Riccardo
R
Urbani
Serena
S
Jeffery
Rosemary
R
Poulsom
Richard
R
Martini
Alessandro
A
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
D000071916:AC133 Antigen; D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D007612:Kanamycin