title: Bone-marrow-derived cells that home to acoustic deafened cochlea preserved their hematopoietic identity.
abstract: The high degree of bone marrow cell (BMC) plasticity has prompted us to test its restoration possibility in inner ear repair. Our aim was to determine the potential of these cells to transdifferentiate into specialized cochlea cell types after acoustic injury and BMC mobilization. Lethally irradiated mice were transplanted with BMCs from green fluorescent protein (GFP) transgenic mice and subjected to acoustic deafening 3 months later. In a separate experiment, stem cell factor and granulocyte colony-stimulating factor were administered to test the effect of BMC mobilization on bone marrow-derived cell (BMDC) transdifferentiation. All mice showed almost complete chimerism 3 months after bone marrow transplantation. Upon acoustic trauma, robust BMDC migration was observed in the deafened cochlea. GFP+ cell migration was most prominent during the first week after acoustic deafening, and these cells accumulated significantly at the spiral ligament, perilymphatic compartment walls, and limbus regions. Most of the BMDCs expressed CD45 and CD68 and were identified as macrophages. Upregulation of stromal-derived factor 1 (SDF-1) was also observed in the spiral ligament during the first week after acoustic deafening. Cytokine treatment resulted in increased BMC mobilization in the systemic circulation. However, the presence of any stem cell progenitors or the differentiation of BMDCs into any cell types expressing cochlea sensory, supporting, fibrocytic, or neuronal markers were not detected in the deafened cochlea. In conclusion, we have demonstrated the homing capability of BMDCs to the deafened cochlea, and these cells displayed mature hematopoietic properties without spontaneous transdifferentiation to any cochlea cell types after acoustic trauma or bone marrow mobilization.
authors.affiliation: Delivery of Drugs, Proteins and Genes Group, Institute of Bioengineering and Nanotechnology, Singapore, Singapore.
authors.forename: Brian Tiong Gee
authors.initials: BT
authors.lastname: Tan
authors.forename: Myranda Mui Gek
authors.initials: MM
authors.lastname: Lee
authors.forename: Runsheng
authors.initials: R
authors.lastname: Ruan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D002465:Cell Movement; D054338:Cell Transdifferentiation; D054377:Chemokine CXCL12 / Q000032:analysis; D003051:Cochlea / Q000473:pathology*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000503:physiopathology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D011183:Postoperative Complications / Q000503:physiopathology; D011292:Premedication; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D054377:Chemokine CXCL12; D016179:Granulocyte Colony-Stimulating Factor; D017493:Leukocyte Common Antigens; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C515256:Cxcl12 protein, mouse; C516770:Ptprc protein, mouse