Neural-Induced Human Mesenchymal Stem Cells Promote Cochlear Cell Regeneration in Deaf Guinea Pigs
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Objectives. In mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae. Methods. HMSCs were isolated from the bone marrow which was obtained from the mastoid process during mastoidectomy for ear surgery. Following neural induction with basic fibroblast growth factor and forskolin, we studied the several neural marker and performed electrophysiological analysis. NI-hMSCs were transplanted into the neomycin treated deafened guinea pig cochlea. Engraftment of NI-hMSCs was evaluated immunohistologically at 8 weeks after transplantation. Results. Following neural differentiation, hMSCs expressed high levels of neural markers, ionic channel markers, which are important in neural function, and tetrodotoxin-sensitive voltage-dependent sodium currents. After transplantation into the scala tympani of damaged cochlea, NI-hMSCs-injected animals exhibited a significant increase in the number of SGNs compared to Hanks balanced salt solution-injected animals. Transplanted NI-hMSCs were found within the perilymphatic space, the organ of Corti, along the cochlear nerve fibers, and in the spiral ganglion. Furthermore, the grafted NI-hMSCs migrated into the spiral ganglion where they expressed the neuron-specific marker, NeuN. Conclusion. The results show the potential of NI-hMSCs to give rise to replace the lost cochlear cells in hearing loss mammals.
Abstract
Objectives. In mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae. Methods. HMSCs were isolated from the bone marrow which was obtained from the mastoid process during mastoidectomy for ear surgery. Following neural induction with basic fibroblast growth factor and forskolin, we studied the several neural marker and performed electrophysiological analysis. NI-hMSCs were transplanted into the neomycin treated deafened guinea pig cochlea. Engraftment of NI-hMSCs was evaluated immunohistologically at 8 weeks after transplantation. Results. Following neural differentiation, hMSCs expressed high levels of neural markers, ionic channel markers, which are important in neural function, and tetrodotoxin-sensitive voltage-dependent sodium currents. After transplantation into the scala tympani of damaged cochlea, NI-hMSCs-injected animals exhibited a significant increase in the number of SGNs compared to Hanks balanced salt solution-injected animals. Transplanted NI-hMSCs were found within the perilymphatic space, the organ of Corti, along the cochlear nerve fibers, and in the spiral ganglion. Furthermore, the grafted NI-hMSCs migrated into the spiral ganglion where they expressed the neuron-specific marker, NeuN. Conclusion. The results show the potential of NI-hMSCs to give rise to replace the lost cochlear cells in hearing loss mammals.
참고문헌 (29)
- Holley MC, "Keynote review: the auditory system, hearing loss and potential targets for drug development", Drug Discov Today, 10(19), pp.1269~1282 (2005)
- Warchol ME, "Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans", Science, 259(5101), pp.1619~1622 (1993)
- Ernfors P, "Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice", Int J Dev Biol, 39(5), pp.799~807 (1995)
- Tan J, "Aminoglycoside-induced degeneration of adult spiral ganglion neurons involves differential modulation of tyrosine kinase B and p75 neurotrophin receptor signaling", Am J Pathol, 169(2), pp.528~543 (2006)
- Duan M, "Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity", Proc Natl Acad Sci U S A, 97(13), pp.7597~7602 (2000)
- Izumikawa M, "Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals", Nat Med, 11(3), pp.271~276 (2005)
- Sage C, "Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein", Science, 307(5712), pp.1114~1118 (2005)
- Li H, "Generation of hair cells by stepwise differentiation of embryonic stem cells", Proc Natl Acad Sci U S A, 100(23), pp.13495~13500 (2003)
- Oshima K, "Sound from silence", Nat Med, 11(3), pp.249~250 (2005)
- Kim SS, "Neural induction with neurogenin1 increases the therapeutic effects of mesenchymal stem cells in the ischemic brain", Stem Cells, 26(9), pp.2217~2228 (2008)
- Liechty KW, "Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep", Nat Med, 6(11), pp.1282~1286 (2000)
- Dezawa M, "Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation", J Clin Invest, 113(12), pp.1701~1710 (2004)
- Chen W, "Restoration of auditory evoked responses by human ES-cell-derived otic progenitors", Nature, 490(7419), pp.278~282 (2012)
- Parker MA, "Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells", Hear Res, 232(1-2), pp.29~43 (2007)
- Revoltella RP, "Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise", Cell Transplant, 17(6), pp.665~678 (2008)
- Nishimura K, "Transplantation of mouse induced pluripotent stem cells into the cochlea", Neuroreport, 20(14), pp.1250~1254 (2009)
- Li H, "Pluripotent stem cells from the adult mouse inner ear", Nat Med, 9(10), pp.1293~1299 (2003)
- Jang S, "Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin", BMC Cell Biol, 11(25) (2010)
- 조용범, "Transplantation of Neural Differentiated Human Mesenchymal Stem Cells into the Cochlea of an Auditory-neuropathy Guinea Pig Model", Journal of Korean Medical Science, 26(4), pp.492~498 (2011), 대한의학회
- Selimoglu E, "Aminoglycoside-induced ototoxicity", Curr Pharm Des, 13(1), pp.119~126 (2007)
- Jiang Y, "Neuroectodermal differentiation from mouse multipotent adult progenitor cells", Proc Natl Acad Sci U S A, 100(Suppl 1:), pp.11854~11860 (2003)
- Anghileri E, "Neuronal differentiation potential of human adipose-derived mesenchymal stem cells", Stem Cells Dev, 17(5), pp.909~916 (2008)
- Li GR, "Ion channels in mesenchymal stem cells from rat bone marrow", Stem Cells, 24(6), pp.1519~1528 (2006)
- Sharif S, "The potential use of bone marrow stromal cells for cochlear cell therapy", Neuroreport, 18(4), pp.351~354 (2007)
- Kamiya K, "Mesenchymal stem cell transplantation accelerates hearing recovery through the repair of injured cochlear fibrocytes", Am J Pathol, 171(1), pp.214~226 (2007)
- Matsuoka AJ, "Enhanced survival of bone-marrow-derived pluripotent stem cells in an animal model of auditory neuropathy", Laryngoscope, 117(9), pp.1629~1635 (2007)
- Hu Z, "Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear", Exp Cell Res, 302(1), pp.40~47 (2005)
- Chen X, "Ischemic rat brain extracts induce human marrow stromal cell growth factor production", Neuropathology, 22(4), pp.275~279 (2002)
- Kelly S, "Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex", Proc Natl Acad Sci U S A, 101(32), pp.11839~11844 (2004)