Adipose-derived mesenchymal stem cells differentiate into inner ear hair cells in guinea pigs induced by progressive addition of cytokines

doi:10.3969/j.issn.2095-4344.2014.37.017

Abstract

Abstract:

BACKGROUND: Sensorineural hearing loss is mainly caused by missing or damaged hair cells in the inner ear. Application of adipose-derived mesenchymal stem cells to regenerate inner ear hair cells is an effective treatment for hearing loss.
OBJECTIVE: To explore the feasibility of in vitro inducing adipose-derived mesenchymal stem cells to differentiate into inner ear hair cell-like cells in guinea pigs.
METHODS: Adipose-derived mesenchymal stem cells from guinea pigs were isolated and cultured to the 3rd generation. Cell phenotype was detected using flow cytometry. Cytokines were added for induction and differentiation by stages, including epidermal growth factor, basic fibroblast growth factor, insulin-like growth factor-1, all-trans retinoic acid, brain-derived neurotrophic factor, neurotrophin 3.
RESULTS AND CONCLUSION: Adipose-derived mesenchymal stem cells of guinea pigs cultured in vitro were fusiform and showed a swirled adherent growth. Passage 3 cells were positive for CDCD29 and CD44, but negative for CD34 and CD45. After induction, the cells were positive for nestin and GFAP positive at early stage;after 10-day continuous induction, the cells expressed Myosin VIIa and Math1, specific markers of hair cells, indicating that cytokines can directly induce adipose-derived mesenchymal stem cells to differentiating into inner ear hair cells in guinea pigs.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: adipose tissue, mesenchymal stem cells, guinea pigs, hair cells, auditory, cytokines

CLC Number:

R394.2

Wang Xiao-yan, Li Bing-bing, Zhang En-feng, Bi Xiao-juan, Liu Li-zhong . Adipose-derived mesenchymal stem cells differentiate into inner ear hair cells in guinea pigs induced by progressive addition of cytokines[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(37): 5998-6002.

Figures/Tables 2

References

[1] Stucky SR, Wolf KE, Kuo T.The economic effect of age-related hearing loss: national, state, and local estimates, 2002 and 2030.J Am Geriatr Soc. 2010;58(3): 618-619.
[2] Turner CW, Gantz BJ, Karsten S,et al.Impact of hair cell preservation in cochlear implantation: combined electric and acoustic hearing.Otol Neurotol. 2010;31(8):1227-1232.
[3] Koehler KR, Mikosz AM, Molosh AI,et al.Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature. 2013;500(7461):217-221.
[4] Fu Y, Wang S, Liu Y,et al.Study on neural stem cell transplantation into natural rat cochlea via round window.Am J Otolaryngol. 2009;30(1):8-16.
[5] Durán Alonso MB, Feijoo-Redondo A, Conde de Felipe M,et al. Generation of inner ear sensory cells from bone marrow-derived human mesenchymal stem cells.Regen Med. 2012;7(6):769-783.
[6] Du D, Lou X.Generation of induced pluripotent stem cells from neonatal mouse cochlear cells.Differentiation. 2014; 87(3-4):127-133.
[7] Pauley S, Kopecky B, Beisel K, et al. Stem cells and molecular strategies to restore hearing.Panminerva Med. 2008;50(1):41-53.
[8] 马旭,姜晓丹,张洪钿,等.骨髓源及脂肪源干细胞向神经元样细胞诱导分化潜力的比较研究[J].中华神经医学杂志,2009,8(5): 441-445.
[9] Chen W, Johnson SL, Marcotti W,et al.Human fetal auditory stem cells can be expanded in vitro and differentiate into functional auditory neurons and hair cell-like cells.Stem Cells. 2009;27(5):1196-1204.
[10] Malgrange B, Belachew S, Thiry M,et al.Proliferative generation of mammalian auditory hair cells in culture.Mech Dev. 2002;112(1-2):79-88.
[11] Guan K, Chang H, Rolletschek A,et al.Embryonic stem cell-derived neurogenesis. Retinoic acid induction and lineage selection of neuronal cells.Cell Tissue Res. 2001; 305(2):171-176.
[12] Lendahl U, Zimmerman LB, McKay RD.CNS stem cells express a new class of intermediate filament protein.Cell. 1990;60(4):585-595.
[13] Hu Z, Corwin JT.Inner ear hair cells produced in vitro by a mesenchymal-to-epithelial transition.Proc Natl Acad Sci U S A. 2007;104(42):16675-16680.
[14] Jeon SJ, Oshima K, Heller S,et al.Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells.Mol Cell Neurosci. 2007;34(1):59-68.
[15] Hung SC, Cheng H, Pan CY,et al.In vitro differentiation of size-sieved stem cells into electrically active neural cells.Stem Cells. 2002;20(6):522-529.