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Cytotherapy. 2018 Feb;20(2):189-203. doi: 10.1016/j.jcyt.2017.11.003. Epub 2017 Dec 13.

Human mesenchymal stromal cell therapy for damaged cochlea repair in nod-scid mice deafened with kanamycin.

Author information

1
Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
2
Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy; Foundation Onlus 'Staminali e Vita', Padua, Italy. Electronic address: valeria.franceschini@unibo.it.
3
Foundation Onlus 'Staminali e Vita', Padua, Italy; Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy.
4
Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, Padua, Italy.
5
Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.
6
Foundation Onlus 'Staminali e Vita', Padua, Italy; Institute for Chemical, Physical Processes, Centro Nazionale delle Ricerche (C.N.R.), Pisa, Italy.

Abstract

BACKGROUND:

Kanamycin, mainly used in the treatment of drug-resistant-tuberculosis, is known to cause irreversible hearing loss. Using the xeno-transplant model, we compared both in vitro and in vivo characteristics of human mesenchymal stromal cells (MSCs) derived from adult tissues, bone marrow (BM-MSCs) and adipose tissue (ADSCs). These tissues were selected for their availability, in vitro multipotency and regenerative potential in vivo in kanamycin-deafened nod-scid mice.

METHODS:

MSCs were isolated from informed donors and expanded ex vivo. We evaluated their proliferation capacity in vitro using the hexosaminidase assay, the phenotypic profile using flow-cytometry of a panel of surface antigens, the osteogenic potential using alkaline phosphatase activity and the adipogenic potential using oil-red-O staining. MSCs were intravenously injected in deafened mice and cochleae, liver, spleen and kidney were sampled 7 and 30 days after transplantation. The dissected organs were analyzed using lectin histochemistry, immunohistochemistry, polymerase chain reaction (PCR) and dual color fluorescence in situ hybridization (DC-FISH).

RESULTS:

MSCs showed similar in vitro characteristics, but ADSCs appeared to be more efficient after prolonged expansion. Both cell types engrafted in the cochlea of damaged mice, inducing regeneration of the damaged sensory structures. Several hybrid cells were detected in engrafted tissues.

DISCUSSION:

BM-MSCs and ADSCs showed in vitro characteristics suitable for tissue regeneration and fused with resident cells in engrafted tissues. The data suggest that paracrine effect is the prevalent mechanism inducing tissue recovery. Overall, BM-MSCs and ADSCs appear to be valuable tools in regenerative medicine for hearing loss recovery.

KEYWORDS:

adipose-derived stem cells; bone marrow mesenchymal stromal cells; cochlea; hybrid cells; kanamycin; multipotency; paracrine effect; proliferative capacity; tissue regeneration; xenotransplantation

PMID:
29246648
DOI:
10.1016/j.jcyt.2017.11.003

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