We investigated whether human cord blood CD133+ hematopoietic stem cells (HSC) engraft the cochlea contributing to its repair, in vivo, in nod-scid mice that had been made deaf after treatment with kanamycin and/or intense noise. PCR analysis, using HLA.DQα1 as a marker for the traceability of the engrafted cells, identified human HSC migrated to various organs of the host, particularly liver, spleen and cochlea, providing evidence of engraftment in injured tissues. All the DNA isolated from mice that did not receive a transplant remained negative. Histologic and immunofluorescent staining confirmed that HSC contributed to the ex novo phenotypic recovery of the internal apparatus of the inner ear, stimulating a rapid regeneration of hair cells in the organ of Corti (OC), a different situation to that of the control oto-injured mice that were not transplanted, that remained with seriously damaged or destroyed cochlear tissues. Dual color-FISH analysis detected the presence of both human and mouse centromeres both in separate cells and within a single nucleus. Most chimeric engrafted cells were of entirely human origin. Confocal scan analysis showed also a small number of heterokaryons, possibly derived from fusion of donor with endogenous cells. Within the cochlea, chimeric cells were seen predominantly in zones with abundant mesenchymal cells and fibrocytes, never in hair cells and neurons. These findings demonstrated that trasplanted human HSC migrating to the inner ear of oto-injured mice, contributed, in vivo, to generate new conditions for the phenotypic resumption of the cochlear OC neurons and hair cell loss.

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

CIORBA, Andrea;BERTOLASO, Lucia;MAGOSSO, Sara;HATZOPOULOS, Stavros;LORITO, Guiscardo;GIORDANO, Pietro;SIMONI, Edi;MARTINI, Alessandro
2008

Abstract

We investigated whether human cord blood CD133+ hematopoietic stem cells (HSC) engraft the cochlea contributing to its repair, in vivo, in nod-scid mice that had been made deaf after treatment with kanamycin and/or intense noise. PCR analysis, using HLA.DQα1 as a marker for the traceability of the engrafted cells, identified human HSC migrated to various organs of the host, particularly liver, spleen and cochlea, providing evidence of engraftment in injured tissues. All the DNA isolated from mice that did not receive a transplant remained negative. Histologic and immunofluorescent staining confirmed that HSC contributed to the ex novo phenotypic recovery of the internal apparatus of the inner ear, stimulating a rapid regeneration of hair cells in the organ of Corti (OC), a different situation to that of the control oto-injured mice that were not transplanted, that remained with seriously damaged or destroyed cochlear tissues. Dual color-FISH analysis detected the presence of both human and mouse centromeres both in separate cells and within a single nucleus. Most chimeric engrafted cells were of entirely human origin. Confocal scan analysis showed also a small number of heterokaryons, possibly derived from fusion of donor with endogenous cells. Within the cochlea, chimeric cells were seen predominantly in zones with abundant mesenchymal cells and fibrocytes, never in hair cells and neurons. These findings demonstrated that trasplanted human HSC migrating to the inner ear of oto-injured mice, contributed, in vivo, to generate new conditions for the phenotypic resumption of the cochlear OC neurons and hair cell loss.
R. P., Revoltella; S., Papini; A., Rosellini; M., Michelini; V., Franceschini; Ciorba, Andrea; Bertolaso, Lucia; Magosso, Sara; Hatzopoulos, Stavros; Lorito, Guiscardo; Giordano, Pietro; Simoni, Edi; Ogno, E.; Cilli, M.; R., Saccardi; Urbani, S.; R., Jeffery; R., Poulsom; Martini, Alessandro
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/521799
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