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Spiral ganglion stem cells can be propagated and differentiated into neurons and glia.

Diensthuber M, Zecha V, Wagenblast J, Arnhold S, Edge AS, Stöver T - Biores Open Access (2014)

Bottom Line: Importantly, spiral ganglion sphere cells maintain their major stem cell characteristics after repeated propagation, which enables the culture of spheres for an extended period of time.In this work, we also demonstrate that differentiated sphere-derived cell populations not only adopt the immunophenotype of mature spiral ganglion cells but also develop distinct ultrastructural features of neurons and glial cells.Thus, our work provides further evidence that self-renewing spiral ganglion stem cells might serve as a promising source for the regeneration of lost auditory neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Frankfurt am Main , Goethe University, Frankfurt am Main, Germany . ; Department of Otology and Laryngology, Harvard Medical School , Boston, Massachusetts. ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary , Boston, Massachusetts.

ABSTRACT
The spiral ganglion is an essential functional component of the peripheral auditory system. Most types of hearing loss are associated with spiral ganglion cell degeneration which is irreversible due to the inner ear's lack of regenerative capacity. Recent studies revealed the existence of stem cells in the postnatal spiral ganglion, which gives rise to the hope that these cells might be useful for regenerative inner ear therapies. Here, we provide an in-depth analysis of sphere-forming stem cells isolated from the spiral ganglion of postnatal mice. We show that spiral ganglion spheres have characteristics similar to neurospheres isolated from the brain. Importantly, spiral ganglion sphere cells maintain their major stem cell characteristics after repeated propagation, which enables the culture of spheres for an extended period of time. In this work, we also demonstrate that differentiated sphere-derived cell populations not only adopt the immunophenotype of mature spiral ganglion cells but also develop distinct ultrastructural features of neurons and glial cells. Thus, our work provides further evidence that self-renewing spiral ganglion stem cells might serve as a promising source for the regeneration of lost auditory neurons.

No MeSH data available.


Related in: MedlinePlus

Morphological features of neural progenitors and spheres. (A, B) High magnification of single spiral ganglion-derived progenitor cell and a developing spiral ganglion sphere reveals the presence of microspikes on their surfaces (arrows)—a characteristic feature of neural progenitors and young neurospheres isolated from the murine brain. To demonstrate the analogy, examples of a neural progenitor cell and a neurosphere derived from the brain is shown in (C) and (D). Images are taken on day in vitro (DIV) 1 (progenitor cells) and after 4 DIV (spheres). (E) Typical appearance of spiral ganglion spheres after a 7-day culture period. (F) Scanning electron microscopy of a spiral ganglion sphere composed of many proliferating single cells. Scale bar=100 μm in B and D, 50 μm in A, C, and F, 200 μm in E.
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f2: Morphological features of neural progenitors and spheres. (A, B) High magnification of single spiral ganglion-derived progenitor cell and a developing spiral ganglion sphere reveals the presence of microspikes on their surfaces (arrows)—a characteristic feature of neural progenitors and young neurospheres isolated from the murine brain. To demonstrate the analogy, examples of a neural progenitor cell and a neurosphere derived from the brain is shown in (C) and (D). Images are taken on day in vitro (DIV) 1 (progenitor cells) and after 4 DIV (spheres). (E) Typical appearance of spiral ganglion spheres after a 7-day culture period. (F) Scanning electron microscopy of a spiral ganglion sphere composed of many proliferating single cells. Scale bar=100 μm in B and D, 50 μm in A, C, and F, 200 μm in E.

Mentions: We microdissected the spiral ganglia of early postnatal mice (Fig. 1A–D) and isolated stem cells from this inner ear organ by their ability to form neurospheres. After 3–5 days free-floating spherical clusters formed from single cells in this defined, serum-free suspension culture system. The morphology of the spiral ganglion-derived spheres resembled the appearance of neurospheres that can be isolated from distinct areas of the brain. The spheres consisted of densely packed cells and displayed a round or oval shape and a grape-like structure (Fig. 2B,E,F). When we screened the surface of single progenitor cells and spheres at high magnification, we detected microspikes (filopodia) (Fig. 2A,B), which have been previously described as a typical morphological feature of neural progenitors and young, viable neurospheres from the brain (Fig. 2C,D).26–28 Ultrastructural analysis of spiral ganglion-derived spheres showed pseudopodia-like cell processes on cells in the spheres' periphery and plentiful mitochondria in the sphere cells indicative of high proliferative activity of the cell colonies (Fig. 3).


Spiral ganglion stem cells can be propagated and differentiated into neurons and glia.

Diensthuber M, Zecha V, Wagenblast J, Arnhold S, Edge AS, Stöver T - Biores Open Access (2014)

Morphological features of neural progenitors and spheres. (A, B) High magnification of single spiral ganglion-derived progenitor cell and a developing spiral ganglion sphere reveals the presence of microspikes on their surfaces (arrows)—a characteristic feature of neural progenitors and young neurospheres isolated from the murine brain. To demonstrate the analogy, examples of a neural progenitor cell and a neurosphere derived from the brain is shown in (C) and (D). Images are taken on day in vitro (DIV) 1 (progenitor cells) and after 4 DIV (spheres). (E) Typical appearance of spiral ganglion spheres after a 7-day culture period. (F) Scanning electron microscopy of a spiral ganglion sphere composed of many proliferating single cells. Scale bar=100 μm in B and D, 50 μm in A, C, and F, 200 μm in E.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4048968&req=5

f2: Morphological features of neural progenitors and spheres. (A, B) High magnification of single spiral ganglion-derived progenitor cell and a developing spiral ganglion sphere reveals the presence of microspikes on their surfaces (arrows)—a characteristic feature of neural progenitors and young neurospheres isolated from the murine brain. To demonstrate the analogy, examples of a neural progenitor cell and a neurosphere derived from the brain is shown in (C) and (D). Images are taken on day in vitro (DIV) 1 (progenitor cells) and after 4 DIV (spheres). (E) Typical appearance of spiral ganglion spheres after a 7-day culture period. (F) Scanning electron microscopy of a spiral ganglion sphere composed of many proliferating single cells. Scale bar=100 μm in B and D, 50 μm in A, C, and F, 200 μm in E.
Mentions: We microdissected the spiral ganglia of early postnatal mice (Fig. 1A–D) and isolated stem cells from this inner ear organ by their ability to form neurospheres. After 3–5 days free-floating spherical clusters formed from single cells in this defined, serum-free suspension culture system. The morphology of the spiral ganglion-derived spheres resembled the appearance of neurospheres that can be isolated from distinct areas of the brain. The spheres consisted of densely packed cells and displayed a round or oval shape and a grape-like structure (Fig. 2B,E,F). When we screened the surface of single progenitor cells and spheres at high magnification, we detected microspikes (filopodia) (Fig. 2A,B), which have been previously described as a typical morphological feature of neural progenitors and young, viable neurospheres from the brain (Fig. 2C,D).26–28 Ultrastructural analysis of spiral ganglion-derived spheres showed pseudopodia-like cell processes on cells in the spheres' periphery and plentiful mitochondria in the sphere cells indicative of high proliferative activity of the cell colonies (Fig. 3).

Bottom Line: Importantly, spiral ganglion sphere cells maintain their major stem cell characteristics after repeated propagation, which enables the culture of spheres for an extended period of time.In this work, we also demonstrate that differentiated sphere-derived cell populations not only adopt the immunophenotype of mature spiral ganglion cells but also develop distinct ultrastructural features of neurons and glial cells.Thus, our work provides further evidence that self-renewing spiral ganglion stem cells might serve as a promising source for the regeneration of lost auditory neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Frankfurt am Main , Goethe University, Frankfurt am Main, Germany . ; Department of Otology and Laryngology, Harvard Medical School , Boston, Massachusetts. ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary , Boston, Massachusetts.

ABSTRACT
The spiral ganglion is an essential functional component of the peripheral auditory system. Most types of hearing loss are associated with spiral ganglion cell degeneration which is irreversible due to the inner ear's lack of regenerative capacity. Recent studies revealed the existence of stem cells in the postnatal spiral ganglion, which gives rise to the hope that these cells might be useful for regenerative inner ear therapies. Here, we provide an in-depth analysis of sphere-forming stem cells isolated from the spiral ganglion of postnatal mice. We show that spiral ganglion spheres have characteristics similar to neurospheres isolated from the brain. Importantly, spiral ganglion sphere cells maintain their major stem cell characteristics after repeated propagation, which enables the culture of spheres for an extended period of time. In this work, we also demonstrate that differentiated sphere-derived cell populations not only adopt the immunophenotype of mature spiral ganglion cells but also develop distinct ultrastructural features of neurons and glial cells. Thus, our work provides further evidence that self-renewing spiral ganglion stem cells might serve as a promising source for the regeneration of lost auditory neurons.

No MeSH data available.


Related in: MedlinePlus