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.
| Language | English |
|---|---|
| Pages | 665-678 |
| Number of pages | 14 |
| Journal | Cell Transplantation |
| Volume | 17 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2008 |
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Keywords
- Cochlea repair
- Deafness
- Organ of corti
- Stem cell
- Transplantation
ASJC Scopus subject areas
- Cell Biology
- Transplantation
- Biomedical Engineering
Cite this
Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise. / Revoltella, Roberto P.; Papini, Sandra; Rosellini, Alfredo; Michelini, Monica; Franceschini, Valeria; Ciorba, Andrea; Bertolaso, Lucia; Magosso, Sara; Hatzopoulos, Stavros; Lorito, Guiscardo; Giordano, Pietro; Simoni, Edi; Ognio, Emanuela; Cilli, Michele; Saccardi, Riccardo; Urbani, Serena; Jeffery, Rosemary; Poulsom, Richard; Martini, Alessandro.
In: Cell Transplantation, Vol. 17, No. 6, 2008, p. 665-678.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise
AU - Revoltella, Roberto P.
AU - Papini, Sandra
AU - Rosellini, Alfredo
AU - Michelini, Monica
AU - Franceschini, Valeria
AU - Ciorba, Andrea
AU - Bertolaso, Lucia
AU - Magosso, Sara
AU - Hatzopoulos, Stavros
AU - Lorito, Guiscardo
AU - Giordano, Pietro
AU - Simoni, Edi
AU - Ognio, Emanuela
AU - Cilli, Michele
AU - Saccardi, Riccardo
AU - Urbani, Serena
AU - Jeffery, Rosemary
AU - Poulsom, Richard
AU - Martini, Alessandro
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Cochlea repair
KW - Deafness
KW - Organ of corti
KW - Stem cell
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=44849126461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44849126461&partnerID=8YFLogxK
U2 - 10.3727/096368908786092685
DO - 10.3727/096368908786092685
M3 - Article
VL - 17
SP - 665
EP - 678
JO - Cell Transplantation
T2 - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 6
ER -